• We are sorry, but NCBI web applications do not support your browser and may not function properly. More information
Logo of nihpaAbout Author manuscriptsSubmit a manuscriptNIH Public Access; Author Manuscript; Accepted for publication in peer reviewed journal;
Cell Mol Life Sci. Author manuscript; available in PMC Dec 4, 2011.
Published in final edited form as:
PMCID: PMC3229932

High molecular weight FGF2: the biology of a nuclear growth factor


Fibroblast growth factor 2 (FGF2) is one of the most studied growth factors to date. Most attention has been dedicated to the smallest, 18kDa FGF2 variant that is released by cells and acts through activation of cell-surface FGF-receptor tyrosine kinases. There are, however, several higher molecular weight (HMW) variants of FGF2 that rarely leave their producing cells, are retained in the nucleus and act independently of FGF-receptors (FGFR). Despite significant evidence documenting the expression and intracellular trafficking of HMW FGF2, many important questions remain about the physiological roles and mechanisms of action of HMW FGF2. In this review, we summarize the current knowledge about the biology of HMW FGF2, its role in disease and areas for future investigation.

Keywords: High molecular weight, FGF2, nuclear, signalling, Api5, SMN

The biogenesis of HMW FGF2

FGF2 is a growth factor that exists in several isoforms differing in their N-terminal extensions, subcellular distribution and function. The smallest, an 18kDa FGF2 low molecular weight (LMW) variant is released by cells and acts through activation of cell-surface FGF-receptors, whereas the HMW (22, 22.5, 24 and 34 kDa) FGF2s localize to the nucleus and signal independently of FGFR [1, 2]. This review will focus specifically on nuclear HMW FGF2 signalling, its molecular mechanisms and its physiological and pathological function.

Regulation of FGF2 transcription and translation

The biogenesis of HMW FGF2 is complex and regulated at both transcriptional and translational levels. FGF2 transcription yields several mRNAs that differ in the length of their large 3′-untranslated region (UTR). Analysis of five different FGF2 mRNA 3′-UTRs revealed profound differences in their stability, leading to discovery of a 122-nt long destabilizing element located upstream of the second poly(A) site as well as a translational enhancer between the fourth and eighth poly(A) sites, which not only enhances the global translation of FGF2 but also selectively upregulates the translation of HMW FGF2 variants [3, 4] (Fig. 1A). The longest UTR is used by primary cells, in contrast to short UTRs preferred by transformed cells in vitro, allowing for precise post-transcriptional regulation of FGF2 production in primary cells in contrast to transformed cells that express FGF2 in a constitutive manner, perhaps contributing to their transformed phenotype [3, 4].

Figure 1
The biogenesis of FGF2 and its regulation. (A) FGF2 transcription yields up to five transcripts differing in the length of their 3′ UTR. This UTR contains several elements regulating transcript stability, with the longest transcript being the ...

In addition to the long 3′-UTR, the 5′-UTR leader of FGF2 mRNA is also lengthy, measuring 485 nt in humans. Analysis of this sequence revealed three additional potential CUG initiation codons (positions 320, 347 and 362 nt from the 5′-end) in frame with the AUG-initiated open reading frame (ORF) (positioned 485 nt from the 5′-end) coding for 18 kDa LMW FGF2, which originally seemed to be the only bioactive variant of FGF2 [5]. The CUG initiation codons give rise to three additional high molecular weight FGF2 variants (22, 22.5 and 24 HMW FGF2) [6, 7]. Later, a fifth FGF2 variant (34 kDa HMW FGF2) was described being initiated from a CUG at position 86 from the 53-end [8], although this variant appears poorly translated in normal conditions. Thus, a single FGF2 mRNA can give rise to a total of five protein variants through a process of alternative translation, with the HMW FGF2 s being linear N-terminal extensions of the LMW 18 kDa variant (Fig. 1A).

How is the translation of FGF2 variants regulated? According to the current model of translation, the 40S ribosomal subunit is first recruited to the 5′-end cap structure of the mRNA, followed by linear scanning of the mRNA sequence in the 3′ direction until an initiation codon in a favorable sequence context is found. This so-called cap-dependent translation has severe limitations when mRNA forms stable secondary structures between two or more initiation codons that cannot be easily linearized by eIF4A RNA helicase [9]. In the case of FGF2, its 485 nt 5′-UTR is not only unusually long but also more than 80 % GC-rich in some regions permitting the formation of a stable secondary structure that prevents ribosomal scanning [9]. Therefore, an alternative mechanism exists to allow for translation of the four FGF2 variants located downstream of the 34 kDa HMW FGF2, which is the only variant of FGF2 translated in a cap-dependent manner due to its proximity to the 5′-end of the mRNA [8]. Vagner et al. showed that 18 kDa LMW FGF2 as well as the 22, 22.5 and 24 kDa HMW variants of FGF2 are translated independently of the cap mechanism and that this process requires a sequence element located between nt 154 and 319 of the FGF2 leader, which has features of an internal ribosomal entry site (IRES) [10]. According to the IRES translational initiation model, the ribosomal 40S subunit binds FGF2 RNA internally at the IRES site located between 154 and 319 nt of the FGF2 5′-UTR to allow translation of both HMW and LMW FGF2. Further analyses revealed two additional factors contributing to the FGF2 IRES activity. First, an intramolecular G-quartet motif, located between nt 57 – 108, functions as a cis-acting positive translational element. Second, ribonucleoprotein hnRNP-A1 binds the IRES and is required for IRES-dependent FGF2 translation, functioning as an IRES trans-acting factor [9, 11].

As the FGF2 IRES is positioned just upstream of the four FGF2 ORFs, it is unlikely to regulate the relative translation of the different FGF2 variants [10]. The IRES alone can not fully explain profound differences in expression of FGF2 variants observed in human aortic epithelial cells, skin fibroblasts or chondrocytes that express either 18 kDa LMW FGF2 alone or all four (LMW and HMW) FGF2 variants depending on the cultivation conditions [1214] (Fig. 1B). This could be a result of the existence of a second IRES located between HMW and LMW FGF2 initiation codons; however this option was ruled out [9]. At this time, the factors that regulate selective translation of HMW FGF2 variants are yet to be identified, although the cap-binding protein eIF-4E may play a role in this process [13, 15].

Subcellular distribution of the FGF2 variants

Growth factors are typically protein molecules that are released from a producer cell and signal via activation of their cognate receptors located at the surface of the recipient cell. Among the FGF2 variants, LMW 18 kDa FGF2 acts according to this paradigm, being released from cells through an unclear mechanism that is independent of the endoplasmic reticulum (ER)-Golgi system, involves exocytosis and requires ATP [1618]. Although HMW FGF2 s can also be released by cells [18], these variants are mostly intracellular and accumulate in the nucleus after translation [19, 20]. The profound differences in the intracellular sorting of the FGF2 variants appear to be the major determinant of their functional diversity, with LMW FGF2 being an extracellular signalling molecule that acts via activation of transmembrane FGFR, whereas the HMW FGF2 variants serve a nuclear, FGFR-independent intracrine function [2].

In addition to HMW FGF2 s, a fraction of both exogenous and endogenous LMW FGF2 can also reach the nucleus, together with internalized cell-surface FGFR and/or complexed with the microtubule-associated translokin [2127]. To distinguish between the nuclear signalling of HMW FGF2 and LMW FGF2, it is at first important to note the differences in their distribution within the nucleus. In Schwann cells or NIH3T3 cells, the LMW FGF2 showed highly ordered localization into the Cajal bodies and nucleoli, whereas HMW FGF2 was distributed in a punctuate pattern in the nucleoplasm and periphery of nucleoli, and co-localized with DNA and mitotic chromosomes [28, 29].

Such differences are likely to originate from different routes of translocation, i.e. translokin- and/or FGFR-dependent in case of extracellular LMW FGF2, FGFR-independent in case of cytoplasmic HMW FGF2; and/or from different nuclear localization signals (NLS) in the HMW and LMW FGF2 sequences. Analyses of FGF2 deletion mutants revealed a total of three NLSs. Two are located at the C-terminus of FGF2, between amino acids 116–129 and 147–155 of LMW FGF2 [27, 30] (Fig. 1A). In addition to the C-terminal NLSs that are present in all FGF2 variants, the N-terminal extension of HMW FGF2 contains a potent NLS as well. When the N-terminal extension was fused to beta-galactosidase, chloramphenicol acetyl-transferase or pyruvate kinase, the resulting chimeric protein also accumulated in the nucleus demonstrating that the N-terminal extension contains a NLS sufficient for nuclear translocation of HMW FGF2 [20, 31, 32]. This NLS lies within the evolutionary conserved glycine-arginine repeat motif within an N-terminal extension of HMW FGF2 [32, 33], that contains several methylated arginine residues. This methylation appears required for efficient HMW FGF2 nuclear localization [3436].

Cell and tissue phenotypes modulated by HMW FGF2

The overlap of HMW and LMW FGF2 actions

Differential intracellular sorting determines the functional differences between LMW and HMW FGF2 rather than intrinsic differences in protein capabilities [2]. For example, in endothelial cells or cardiomyocytes, exogenously added HMW FGF2 behaved similarly to LMW FGF2 in FGFR or heparin binding, activation of ERK kinase, stimulation of rRNA synthesis, and induction of both cell proliferation and chemotactic movement [37, 38]. LMW FGF2, on the other hand, can mimic the HMW FGF2 phenotypes, such as growth in low serum conditions, when artificially targeted to the nucleus [29].

As many common in vitro cell models expressing HMW FGF2 also seem to export it [18, 3941] (P. Krejci, unpublished), the exogenous signalling of HMW FGF2 (i.e. LMW FGF2-mimicking) is very likely contributing to the observed phenotypes of putative nuclear HMW FGF2 signalling. It is unclear to what extent extracellular HMW FGF2 exists naturally in vivo, although its release from over-expressing and/or dying cells was documented in at least one pathological condition, hairy cell leukemia [42]. In this section, we will discuss the cell- and tissue-phenotypes that appear to be regulated by HMW FGF2 nuclear signalling.

HMW FGF2 expression and cellular actions in vitro

HMW FGF2 expression is relatively common in vitro, being detected in cultured cells of bone, cartilage, endothelial, blood, neuronal, glial and liver origin [13, 14, 39, 4347]. This ubiquitous expression may represent an adaptation to in vitro culture, as primary cells seem to express only LMW FGF2 in contrast to transformed cells that express both LMW and HMW FGF2 [12]. In our experiments, freshly isolated murine heart, muscle, skin, lung, spleen and kidney cells all upregulated HMW FGF2 within the first week of in vitro cultivation (P. Krejci and W. R. Wilcox, unpublished). Similarly, human fetal chondrocytes upregulate HMW FGF2 expression within 48 hours after transition to tissue culture [14] (Fig. 1B).

To date, the effects of HMW FGF2 have been examined in only a limited number of cell types in vitro (Table 1). While these cells were scored for HMW FGF2 influence on the basic cell culture characteristics such as proliferation, migration, and apoptosis, the effect of HMW FGF2 on other, more cell-type specific functions remains largely unknown. Similarly, our knowledge of the mechanism of HMW FGF2 signalling in cells is poor, with the molecular basis of the cell phenotypes mediated by HMW FGF2 being mostly undefined.

Table 1
HMW FGF2 cellular actions in vitro.

The proliferative activity of HMW FGF2 has been well documented in NIH3T3 and A31 fibroblasts, adult bovine aortic endothelial (ABAE) cells, cardiac myocytes and ROS17/2.8 osteosarcoma cells [39, 4853]. In NIH3T3 cells, this proliferation also takes place in low-serum conditions [29, 49, 50]. In addition to proliferation, HMW FGF2 induces a phenotype of radioresistance in NIH3T3 cells as well as HeLa cervical cancer cells, which is accompanied by G2 delay and hypophosphorylation of p34cdc2 kinase in the latter cells [50, 54].

Little is known about HMW FGF2 effect on cell differentiation. HMW FGF2 appears to influence cell fate decisions in human embryonal stem cells (hESC), where its expression is downregulated upon differentiation, and its knock-down in undifferentiated cells induces differentiation [55] (P. Dvorak, unpublished). In cultured avian Schwann cell precursors isolated from the neural crest, HMW FGF2 caused trans-differentiation into melanocytes [56]. In rat calvarial osteoblasts, the expression of HMW FGF2 increased as the cell-state became more differentiated [57]. In contrast, over-expression of HMW FGF2 failed to induce differentiation in a PC12 in vitro cell model of neuronal differentiation [58].

HMW FGF2 expression and phenotypes in vivo

The in vivo expression pattern of HMW FGF2 is poorly defined to date, although it is more relevant than in vitro expression. FGF2 transcripts are found in most developing and adult human tissues including brain, heart, lung, skeletal muscle, pancreas and others [59], but limited data is available about HMW FGF2 expression in these tissues. In transgenic mice expressing bicistronic luciferase vector capable of monitoring the activity of the FGF2 IRES, IRES activity was limited to the adult brain and testis, suggesting a restricted expression of FGF2 protein in vivo [60]. Furthermore, the HMW FGF2 expression may be absent or restricted even in tissues that produce FGF2 protein. In human epiphyseal growth plate cartilage, HMW FGF2 is expressed only by proliferating chondrocytes in contrast to LMW FGF2 that is produced throughout the growth plate [14]. In addition to cartilage, HMW FGF2 was found in heart, aorta, testis, lung, brain, peripheral nerves, adrenal gland and eye tissue [6167].

Several studies addressing the function of HMW FGF2 in vivo have been performed to date (Table 2). LMW and HMW FGF2 both stimulate endothelial cell proliferation but differ in their effect on cell migration, which is increased by LMW FGF2 in contrast to HMW FGF2 that has an inhibitory effect [40]. This inhibition requires an estrogen receptor and is mediated by the amino terminal extension of 24 kDa HMW FGF2 [68, 69]. Moreover, a recent study reports a thrombin-mediated cleavage of the amino terminal extension of HMW FGF2. This abolishes its inhibitory effect on endothelial cell migration [70], thus adding another level of regulation of the exogenous HMW FGF2. The HMW FGF2-mediated inhibition of endothelial cell migration was confirmed in vivo [69, 71] and one physiological role of HMW FGF2 may lie in the negative regulation of angiogenesis.

Table 2
HMW FGF2 cell/tissue actions in vivo.

In cardiac muscle, HMW FGF2 accumulates upon the exposure to stressful stimuli such as isopreterenol or hypothyroidism [72, 61]. When injected into the infarcted rat heart, HMW FGF2 but not LMW FGF2 induced significant cardiac hypertrophy by increasing the overall size of cardiomyocytes, possibly via induction of cardiotrophin-1 [38, 73].

The brain is a prominent site of FGF2 expression, with HMW FGF2 being found in the spinal cord, cerebellum, cortex and substantia nigra [62, 64, 74, 75]. In vitro, exogenously added HMW FGF2 showed neurotrophic activity on cultures of dopaminergic neurons isolated from rat mesencephalon [76]. This was confirmed in vivo, where HMW FGF2, released from implanted Schwann cells, enhanced the regeneration of injured rat sciatic nerve [77, 78]. Similar results were obtained when dopaminergic neurons were implanted with HMW FGF2-overexpressing Schwann cells into the injured rat brain, again confirming the neurotrophic activity of HMW FGF2 [75]. As the HMW FGF2 effects on both cardiomyocytes and neurons were induced by extracellular HMW FGF2, it is difficult to conclude to what extent such effects were mediated solely by nuclear HMW FGF2 signalling because of concomitant activation of FGFR-dependent signalling pathways.

There are two studies that report the in vivo effect of HMW FGF2 likely mediated by its nuclear signalling. Thomas-Mudge at al. [79] engineered NBTII rat bladder carcinoma cells to express 24kDa HMW FGF2 under the control of a conditional doxycycline promoter. When such cells were inoculated into nude mice, they gave rise to lung metastases in comparison with their FGF2 non-expressing counterparts, which underwent rapid apoptosis.

Garmy-Susini et al. [67] described a HMW FGF2 role in the effects of the sex hormone estradiol. Estradiol promoted angiogenesis and endothelial cell migration and proliferation in the Fgf2+/+ mice but not Fgf2−/− animals. This phenotype was rescued in mice expressing intact HMW FGF2 but not LMW FGF2 (Fgf2lmw−/−), thus demonstrating that HMW FGF2 but not LMW FGF2 signalling is necessary for positive effects of estradiol on the epithelia.

HMW FGF2 in disease

Unlike FGF23 [80], there is not yet a disease known to be associated with mutations in HMW FGF2, nor FGF2 in general. There are however two conditions where HMW FGF2 appears to play a pathophysiological role in vivo, B-cell chronic lymphoid leukemia (BCLL) and hairy cell leukemia (HCL).

BCLL is the most prevalent leukemia in Europe and North America and is characterized by accumulation of mature B-lymphocytes that have escaped apoptosis and undergone cell-cycle arrest in the G0/G1 phase of the cell cycle [81]. In patients suffering from BCLL, plasma FGF2 is massively upregulated when compared to controls, which correlates with the overexpression of both LMW and HMW FGF2 in the leukemic clone in vivo [82, 83]. While extracellular LMW FGF2 has no known autocrine function in BCLL to date [82], the intracellular HMW FGF2 content shows a strong positive correlation with the aggressiveness of disease and protects BCLL cells from experimentally-induced apoptosis [84]. HCL is a B-cell malignancy similar to BCLL [81]. The FGF2 abnormalities in HCL also resemble those of BCLL, including the importance of FGF2 for resistance to cytotoxic drugs and survival of HCL cells [42].

The molecular mechanism of HMW FGF2 action

In AR4–2J pancreatic cancer cells, expression of HMW FGF2 induces growth in low-serum conditions and is accompanied by changes in protein kinase C isoform expression and activation of extracellular signal-regulated kinase-mitogen activated protein (ERK MAP) kinase, both independent of FGFR [85]. In HMW FGF2-expressing NIH3T3 fibroblasts, the transcription of a total of 77 genes was significantly up or down-regulated when compared to LMW FGF2-expressing cells, including genes acting in the cell cycle, chromatin remodelling, transcription and cell adhesion [86]. How are these effects achieved? To date, the molecular basis underlying the intracrine signalling of HMW FGF2 remains poorly characterized.

Partners of HMW FGF2

Antiapoptotic protein 5 (Api5; FIF; AAC11)

Api5 is a nuclear protein originally identified based on its strong antiapoptotic properties [87, 88]. The Api5 transcript generates two proteins, the 55 kDa full-length Api5 and a 25 kDa, N-terminally truncated variant [89]. Api5 is highly expressed in various transformed cell lines in vitro and enhances matrix metalloproteinase expression, matrigel invasion and laminin adhesion in the cervical cancer model cell line CUMC6 [45, 88]. Two experimental studies have shown the potent anti-apoptotic action of Api5. Wild-type BALB/c3T3 cultures die in serum-free media in 10 days in contrast to Api5 expressing cells that survived for up to 16 weeks in the same conditions [87]. Similarly, cultured cervical cancer cells showed significantly increased survival in serum-free media when expressing Api5 [88].

Using a yeast two-hybrid system, the interaction of Api5 with FGF2 was identified [89]. Api5 showed stronger affinity for HMW FGF2 than LMW FGF2 and did not interact with FGF1, FGF3 or FGF6. Similar to Api5, HMW FGF2 has a pro-survival action in various experimental models [54, 79], implying that both HMW FGF2 and Api5 functionally cooperate. This is further suggested by our recent finding that Api5 upregulation correlates with HMW FGF2 overexpression in BCLL [83] (see section 2.4.).

As mentioned earlier (section 2.3.), HMW FGF2 plays an essential role in estradiol-mediated angiogenesis in vivo and endothelial cell migration and proliferation in vitro. RNAi-mediated downregulation of Api5 completely abolishes the effect of estradiol on endothelial cell migration in the presence of HMW FGF2, thus clearly demonstrating the functional cooperation between FGF2 and Api5 in this process [67].

Ribosomal protein L6/TAXREB107

Although both LMW and HMW FGF2 associate with the ribosomal fraction in the nucleus, this association is much more prevalent for HMW FGF2, suggesting a function of the N-terminal extension in this phenotype [19, 90]. Within the ribosome, HMW FGF2 appears to interact with the L6/TAXREB107 protein that functions as both a ribosomal component and a member of the cAMP response element binding protein/activating transcription factor (CREB/ATF) family. The HMW FGF2-L6/TAX-REB107 interaction takes place between the N-terminal extension of HMW FGF2 and C-terminal region of L6/TAXREB107 and suggests a role of HMW FGF2 in ribosome biogenesis and translational control [91].

Splicing factor SF3a66 and survival of motor neurons protein (SMN)

Using a yeast two-hybrid approach, Gringel et al. [92] found an interaction of FGF2 with the splicing factor SF3a66. This interaction took place between the core sequence common to all FGF2 variants and the C-terminal region of SF3a66.

SMN is a 38 kDa protein that localizes to both the cytoplasm and the nucleus and functions as an essential factor in spliceosomal ribonucleoprotein assembly [93]. Inactivation of SMN causes spinal muscular atrophy, manifested by progressive degeneration of the motor neurons of the spinal cord and early death [94].

The interaction between HMW FGF2 and SMN was found in co-immunoprecipitation experiments, addressing the hypothesis that SMN, known to bind the GR-rich proteins, interacts with the GR-rich region of HMW FGF2 [28]. Further analyses showed that HMW FGF2, but not LMW FGF2, binds directly to the N-terminus of SMN between amino acids 1–90, which constitutes a domain involved in interaction with both RNA and spliceosomal proteins such as Gemin2/SIP2 [28, 95]. Given the essential role of both SF3a66 and SMN in the assembly of spliceosomal complexes, one of intracellular roles of HMW FGF2 may lie in the modulation of splicing.

Future prospects

Despite significant evidence documenting the biological activities of HMW FGF2, many important questions remain. These relate mostly to the physiological role of HMW FGF2 as well as to the molecular basis of its action. At the level of translation, it is not yet clear how HMW FGF2 translation is regulated following the general activation of the FGF2 IRES (Fig. 1B). Thus one specific area of future research lies in the identification of factors that govern the differential translation of the FGF2 variants.

Another important area is to understand the role of HMW FGF2 in vivo. Generation and detailed analysis of transgenic mice expressing LMW but not HMW FGF2 (Fgf hmw−/−) should identify possible physiological functions of HMW FGF2 in vivo. As FGF2 is one of the most significant factors that maintain the pluripotency of hESCs, which also express HMW FGF2 in large quantities, self-renewal and early differentiation of hECSs may represent examples of processes potentially regulated by HMW FGF2 in vivo [55, 96].

To understand the physiological role of HMW FGF2 completely, we also need more insights into the molecular mechanisms of its signalling. To date, the role of HMW FGF2 in the estradiol effect on the epithelia represents the only mechanistic evidence of the HMW FGF2 action in vivo [67]. When adapted to in vitro conditions, the HMW FGF2 role in estradiol signalling could serve as an experimental model to address the molecular mechanism of HMW FGF2 signalling in detail, including the functional consequences of HMW FGF2 interaction with its partners such as Api5 or SMN.


This work was supported by the Multiple Myeloma Research Foundation, the Ministry of Education, Youth and Sports of the Czech Republic (MSM0021622430, LC06077), the National Institutes of Health (5P01-HD22657), the Winnick Family Research Scholars Award (WRW) and an EMBO Installation Grant (VB).


1. Yu PJ, Ferrari G, Galloway AC, Mignatti P, Pintucci G. Basic fibroblast growth factor (FGF-2): The high molecular weight forms come of age. J Cell Biochem. 2007;100:1100–1108. [PubMed]
2. S[slash in circle]rensen V, Nilsen T, Więdłocha A. Functional diversity of FGF-2 isoforms by intracellular sorting. BioEssays. 2006;28:504–514. [PubMed]
3. Touriol C, Morillon A, Gensac MC, Prats H, Prats AC. Expression of human fibroblast growth factor 2 mRNA is post-transcriptionally controlled by a unique destabilizing element present in the 3′-untranslated region between alternative polyadenylation sites. J Biol Chem. 1999;274:21402–21408. [PubMed]
4. Touriol C, Roussigne M, Gensac MC, Prats H, Prats AC. Alternative translation initiation of human fibroblast growth factor 2 mRNA controlled by its 3′-untranslated region involves a poly(A) switch and a translational enhancer. J Biol Chem. 2000;275:19361–19367. [PubMed]
5. Gospodarowicz D, Cheng J, Lui GM, Baird A, Böhlent P. Isolation of brain fibroblast growth factor by heparin-Sepharose afinity chromatography: Identity with pituitary fibroblast growth factor. Proc Natl Acad Sci USA. 1984;81:6963–6967. [PMC free article] [PubMed]
6. Florkiewicz RZ, Sommer A. Human basic fibroblast growth factor gene encodes four polypeptides: Three initiate translation from non-AUG codons. Proc Natl Acad Sci USA. 1989;86:3978–3981. [PMC free article] [PubMed]
7. Prats H, Kaghad M, Prats AC, Klagsbrun M, Lelias JM, Liauzun P, Chalon P, Tauber JP, Amalric F, Smith JA, Caput D. High molecular mass forms of basic fibroblast growth factor are initiated by alternative CUG codons. Proc Natl Acad Sci USA. 1989;86:1836–1840. [PMC free article] [PubMed]
8. Arnaud E, Touriol C, Boutonnet C, Gensac MC, Vagner S, Prats H, Prats AC. A new 34-kilodalton isoform of human fibroblast growth factor 2 is cap dependently synthesized by using a non-AUG start codon and behaves as a survival factor. Mol Cell Biol. 1999;19:505–514. [PMC free article] [PubMed]
9. Bonnal S, Schaeffer C, Creancier L, Clamens S, Moine H, Prats AC, Vagner S. A single internal ribosome entry site containing a G quartet RNA structure drives fibroblast growth factor 2 gene expression at four alternative translation initiation codons. J Biol Chem. 2003;278:39330–39336. [PMC free article] [PubMed]
10. Vagner S, Gensac MC, Maret A, Bayard F, Amalric F, Prats H, Prats AC. Alternative translation of human fibroblast growth factor 2 mRNA occurs by internal entry of ribosomes. Mol Cell Biol. 1995;15:35–44. [PMC free article] [PubMed]
11. Bonnal S, Pileur F, Orsini C, Parker F, Pujol F, Prats AC, Vagner S. Heterogeneous nuclear ribonucleo-protein A1 is a novel internal ribosome entry site trans-acting factor that modulates alternative initiation of translation of the fibroblast growth factor 2 mRNA. J Biol Chem. 2005;280:4144–4153. [PubMed]
12. Vagner S, Touriol C, Galy B, Audigier S, Gensac MC, Amalric F, Bayard F, Prats H, Prats AC. Translation of CUG- but not AUG-initiated forms of human fibroblast growth factor 2 is activated in transformed and stressed cells. J Cell Biol. 1996;135:1391–1402. [PMC free article] [PubMed]
13. Galy B, Maret A, Prats AC, Prats H. Cell transformation results in the loss of the density-dependent translational regulation of the expression of fibroblast growth factor 2 isoforms. Cancer Res. 1999;59:165–171. [PubMed]
14. Krejci P, Krakow D, Mekikian PB, Wilcox WR. Fibroblast growth factors 1, 2, 17 and 19 are the predominant FGF ligands expressed in human fetal growth plate cartilage. Ped Res. 2007;61:267–272. [PubMed]
15. Kevil C, Carter P, Hu B, DeBenedetti A. Translational enhancement of FGF-2 by eIF-4 factors, and alternate utilization of CUG and AUG codons for translation initiation. Oncogene. 1995;11:2339–2348. [PubMed]
16. Mignatti P, Morimoto T, Rifkin DB. Basic fibroblast growth factor, a protein devoid of secretory signal sequence, is released by cells via a pathway independent of the endoplasmatic reticulum-Golgi complex. J Cell Physiol. 1992;151:81–93. [PubMed]
17. Florkiewicz RZ, Majack RA, Buechler RD, Florkiewicz E. Quantitative export of FGF-2 occurs through an alternative, energy-dependent, non-ER/Golgi pathway. J Cell Physiol. 1995;162:388–399. [PubMed]
18. Taverna S, Ghersi G, Ginestra A, Rigogliuso S, Pecorella S, Alaimo G, Saladino F, Dolo V, Dell’Era P, Pavan A, Pizzolanti G, Mignatti P, Presta M, Vittorelli ML. Shedding of membrane vesicles mediates fibroblast growth factor-2 release from cells. J Biol Chem. 2003;278:51911–51919. [PubMed]
19. Renko M, Quarto N, Morimoto T, Rifkin DB. Nuclear and cytoplasmic localization of different basic fibroblast growth factor species. J Cell Physiol. 1990;144:108–114. [PubMed]
20. Bugler B, Amalric F, Prats H. Alternative initiation of translation determines cytoplasmic or nuclear localization of basic fibroblast growth factor. Mol Cell Biol. 1991;11:573–577. [PMC free article] [PubMed]
21. Bouche G, Gas N, Prats H, Baldin V, Tauber JP, Teissie J, Amalric F. Basic fibroblast growth factor enters the nucleolus and stimulates the transcription of ribosomal genes in ABAE cells undergoing G0-G1 transition. Proc Natl Acad Sci USA. 1987;84:6770–6774. [PMC free article] [PubMed]
22. Baldin V, Roman AM, Bosc-Bierne I, Amalric F, Bouche G. Translocation of bFGF to the nucleus is G1 phase cell cycle specific in bovine aortic endothelial cells. EMBO J. 1990;9:1511–1517. [PMC free article] [PubMed]
23. Hawker JR, Jr, Granger HJ. Internalized basic fibroblast growth factor translocates to nuclei of venular endothelial cells. Am J Physiol. 1992;262:H1525–1537. [PubMed]
24. Clarke WE, Berry M, Smith C, Kent A, Logan A. Coordination of fibroblast growth factor receptor 1 (FGFR1) and fibroblast growth factor-2 (FGF-2) trafficking to nuclei of reactive astrocytes around cerebral lesions in adult rats. Mol Cell Neurosci. 2001;17:17–30. [PubMed]
25. Bossard C, Laurell H, Van den Berghe L, Meunier S, Zanibellato C, Prats H. Translokin is an intra-cellular mediator of FGF-2 trafficking. Nat Cell Biol. 2003;5:433–439. [PubMed]
26. Stachowiak MK, Fang X, Myers JM, Dunham SM, Berezney R, Maher PA, Stachowiak EK. Integrative nuclear FGFR1 signaling (INFS) as a part of a universal “feed-forward-and-gate” signaling module that controls cell growth and differentiation. J Cell Biochem. 2003;90:662–691. [PubMed]
27. Sheng Z, Lewis JA, Chirico WJ. Nuclear and nucleolar localization of 18-kDa fibroblast growth factor-2 is controled by C-terminal signals. J Biol Chem. 2004;279:40153–40160. [PubMed]
28. Claus P, Döring F, Gringel S, Müller-Ostermeyer F, Fuhlrott J, Kraft T, Grothe C. Differential intranuclear localization of fibroblast growth factor-2 isoforms and specific interaction with the survival of motoneuron protein. J Biol Chem. 2003;278:479–485. [PubMed]
29. Arese M, Chen Y, Florkiewicz RZ, Gualandris A, Shen B, Rifkin DB. Nuclear activities of basic fibroblast growth factor: Potentiation of low-serum growth mediated by natural or chimeric nuclear localization signal. Mol Biol Cell. 1999;10:1429–1444. [PMC free article] [PubMed]
30. Foletti A, Vuadens F, Beermann F. Nuclear localization of mouse fibroblast growth factor 2 requires N-terminal and C-terminal sequences. Cell Mol Life Sci. 2003;60:2254–2265. [PubMed]
31. Quarto N, Finger FP, Rifkin DB. The NH2-terminal extension of high molecular weight bFGF is a nuclear targeting signal. J Cell Physiol. 1991;147:311–318. [PubMed]
32. Dono R, James D, Zeller R. A GR-motif functions in nuclear accumulation of the large FGF-2 isoforms and interferes with mitogenic signaling. Oncogene. 1998;16:2151–2158. [PubMed]
33. Rifkin DB, Moscatelli D, Roghani M, Nagano Y, Quarto N, Klein S, Bikfalvi A. Studies on FGF-2: nuclear localization and function of high molecular weight forms and receptor binding in the absence of heparin. Mol Reprod Dev. 1994;39:102–104. [PubMed]
34. Burgess WH, Bizik J, Mehlman T, Quarto N, Rifkin DB. Direct evidence for methylation of arginine residues in high molecular weight forms of basic fibroblast growth factor. Cell Regul. 1991;2:87–93. [PMC free article] [PubMed]
35. Klein S, Carroll JA, Chen Y, Henry MF, Henry PA, Ortonowski IE, Pintucci G, Beavis RC, Burgess WH, Rifkin DB. Biochemical analysis of the arginine methylation of high molecular weight fibroblast growth factor-2. J Biol Chem. 2000;275:3150–3157. [PubMed]
36. Pintucci G, Quarto N, Rifkin DB. Methylation of high molecular weight fibroblast growth factor-2 determines post-translational increases in molecular weight and affects its intracellular distribution. Mol Biol Cell. 1996;7:1249–1258. [PMC free article] [PubMed]
37. Gualandris A, Urbinati C, Rusnati M, Ziche M, Presta M. Interaction of high-molecular-weight basic fibroblast growth factor with endothelium: biological activity and intracellular fate of human recombinant M(r) 24,000 bFGF. J Cell Physiol. 1994;161:149–159. [PubMed]
38. Jiang ZS, Jeyaraman M, Wen GB, Fandrich RR, Dixon IMC, Cattini PA, Kardami E. High-but not low- molecular weight FGF-2 causes cardiac hypertrophy in vivo; possible involvement of cardiotrophin-1. Mol Cell Cardiol. 2007;42:222–233. [PubMed]
39. Couderc B, Prats H, Bayard F, Amalric F. Potential oncogenic effects of basic fibroblast growth factor requires cooperation between CUG and AUG-initiated forms. Cell Regul. 1991;2:709–718. [PMC free article] [PubMed]
40. Piotrowicz RS, Martin JL, Dillman WH, Levin EG. The 27-kDa heat shock protein facilitates basic fibroblast growth factor release from endothelial cells. J Biol Chem. 1997;272:7042–7047. [PubMed]
41. Wieder R, Wang H, Shirke S, Wang Q, Menzel T, Feirt N, Jakubowski AA, Gabrilove JL. Low level expression of basic FGF upregulates Bcl-2 and delays apoptosis, but high intracellular levels are required to induce transformation in NIH3T3 cells. Growth Factors. 1997;15:41–60. [PubMed]
42. Gruber G, Schwarzmeier JD, Shehata M, Hilgarth M, Berger R. Basic fibroblast growth factor is expressed by CD19/CD11c-positive cells in hairy cell leukemia. Blood. 1999;94:1077–1085. [PubMed]
43. Sobue T, Zhang X, Florkiewicz RZ, Hurley MM. Interleukin-1 regulates FGF-2 mRNA and localization of FGF-2 protein in human osteoblasts. Biochem Biophys Res Commun. 2001;286:33–40. [PubMed]
44. Kamiguchi H, Yoshida K, Wakamoto H, Inaba M, Sasaki H, Otani M, Toya S. Cytokine-induced selective increase of high-molecular-weight bFGF isoforms and their subcellular kinetics in cultured rat hippocampal astrocytes. Neurochem Res. 1996;21:701–706. [PubMed]
45. Krejci P, Faitova J, Laurell H, Hampl A, Dvorak P. FGF-2 expression and its action in human leukemia and lymphoma cell lines. Leukemia. 2003;17:818–820. [PubMed]
46. Krejci P, Mekikian PB, Wilcox WR. The fibroblast growth factors in multiple myeloma. Leukemia. 2006;20:1165–1168. [PubMed]
47. Li A, Guo H, Luo X, Sheng J, Yang S, Yin Y, Zhou J, Zhou J. Apomorphine-induced activation of dopamine receptors modulates FGF-2 expression in astrocytic cultures and promotes survival of dopaminergic neurons. FASEB J. 2006;20:1263–1265. [PubMed]
48. Pasumarthi KBS, Doble BW, Kardami E, Cattini PA. Over-expression of CUG- or AUG-initiated forms of basic fibroblast growth factor in cardiac myocytes results in similar effects on mitosis and protein synthesis but distinct nuclear morphologies. J Mol Cell Cardiol. 1994;26:1045–1060. [PubMed]
49. Bikfalvi A, Klein S, Pintucci G, Quarto N, Mignatti P, Rifkin DB. Differential modulation of cell phenotype by different molecular weight forms of basic fibroblast growth factor: possible intracellular signaling by the high molecular weight forms. J Cell Biol. 1995;129:233–243. [PMC free article] [PubMed]
50. Delrieu I, Arnaud E, Ferjoux G, Bayard F, Faye JC. Overexpression of the FGF-2 24-kDa isoform up-regulates Il-6 transcription in NIH-3T3 cells. FEBS Lett. 1998;436:17–22. [PubMed]
51. Gualandris A, Arese M, Shen B, Rifkin D. Modulation of cell growth and transformation by doxycycline-regulated FGF-2 expression in NIH-3T3 cells. J Cell Physiol. 1999;181:273–284. [PubMed]
52. Dini G, Funghini S, Witort E, Magnelli L, Fanti E, Rifkin DB, Del Rosso M. Overexpression of the 18 kDa and 22/24 kDa FGF-2 isoforms results in differential drug resistence and amplification potential. J Cell Physiol. 2002;193:64–72. [PubMed]
53. Xiao L, Liu P, Sobue T, Lichtler A, Coffin JD, Hurley MM. Effect of overexpressing fibroblast growth factor 2 protein isoforms in osteoblastic ROS 17/2.8 cells. J Cell Biochem. 2003;89:1291–1301. [PubMed]
54. Cohen-Jonathan E, Toulas C, Monteil S, Couderc B, Maret A, Bard JJ, Prats H, Daly-Schveitzer N, Favre G. Radioresistance induced by the high molecular forms of the basic fibroblast growth factor is associated with an increased G2 delay and a hyperphosphorylation of p34CDC2 in HeLa cells. Cancer Res. 1997;57:1364–1370. [PubMed]
55. Dvorak P, Dvorakova D, Koskova S, Vodinska M, Najvirtova M, Krekac D, Hampl A. Expression and potential role of fibroblast growth factor 2 and its receptors in human embryonic stem cells. Stem Cells. 2005;23:1200–1211. [PubMed]
56. Sherman L, Stocker KM, Morrison R, Ciment G. Basic fibroblast growth factor (bFGF) acts intracellularly to cause the transdifferentiation of avian neural crest-derived Schwann cell precursors into melanocytes. Development. 1993;118:1313–1326. [PubMed]
57. Cowan CM, Quarto N, Warren SM, Salim A, Longaker MT. Age-related changes in the biomolecular mechanisms of calvarial osteoblast biology affect fibroblast growth factor-2 signaling and osteogenesis. J Biol Chem. 2003;278:32005–32013. [PubMed]
58. Grothe C, Meisinger C, Holzschuh J, Wewetzer K, Cattini P. Over-expression of the 18 kDa and 21\23 kDa fibroblast growth factor-2 isoforms in PC12 cells and Schwann cells results in altered cell morphology and growth. Mol Brain Res. 1998;57:97–105. [PubMed]
59. Knee RS, Pitcher S, Murphy PR. Basic fibroblast growth factor sense (FGF) and antisense (gfg) RNA transcripts are expressed in unfertilized human oocytes and in differentiated human tissues. Biochem Biophys Res Commun. 1994;205:577–583. [PubMed]
60. Creancier L, Morello D, Mercier P, Prats AC. Fibroblast growth factor 2 internal ribosome entry site (IRES) activity ex vivo and in transgenic mice reveals a stringent tissue-specific regulation. J Cell Biol. 2000;150:275–281. [PMC free article] [PubMed]
61. Liu L, Doble BW, Kardami E. Perinatal phenotype and hypothyroidism are associated with elevated levels of 21.5- to 22-kDa basic fibroblast growth factor in cardiac ventricles. Dev Biol. 1993;157:507–516. [PubMed]
62. Giordano S, Sherman L, Lyman W, Morrison R. Multiple molecular weight forms of basic fibroblast growth factor are developmentally regulated in the central nervous system. Dev Biol. 1992;152:293–303. [PubMed]
63. Teshima-Kondo S, Kondo K, Prado-Lourenco L, Gonzalez-Herrera IG, Rokutan K, Bayard F, Arnal JF, Prats AC. Hyperglycemia upregulates translation of the fibroblast growth factor 2 mRNA in mouse aorta via internal ribosome entry site. FASEB J. 2004;18:1583–1585. [PubMed]
64. Gonzalez-Herrera IG, Prado-Lourenco L, Pileur F, Conte C, Morin A, Cabon F, Prats H, Vagner S, Bayard F, Audigier S, Prats AC. Testosterone regulates FGF-2 expression during testis maturation by an IRES-dependent translational mechanism. FASEB J. 2006;20:476–478. [PubMed]
65. Meisinger C, Grothe C. Differential regulation of fibroblast growth factor (FGF)-2 and FGF receptor 1 mRNAs and FGF-2 isoforms in spinal ganglia and sciatic nerve after peripheral nerve lesion. J Neurochem. 1997;68:1150–1158. [PubMed]
66. Meisinger C, Grothe C. Differential expression of FGF-2 isoforms in the rat adrenal medulla during postnatal development in vivo. Brain Res. 1997;757:291–294. [PubMed]
67. Garmy-Susini B, Delmas E, Gourdy P, Zhou M, Bossard C, Bugler B, Bayard F, Krust A, Prats AC, Doetschman T, Prats H, Arnal JF. Role of fibroblast growth factor-2 isoforms in the effect of estradiol on endothelial cell migration and proliferation. Circ Res. 2004;94:1301–1309. [PubMed]
68. Piotrowicz RS, Ding L, Maher P, Levin EG. Inhibition of cell migration by 24-kDa fibroblast growth factor-2 is dependent upon the estrogen receptor. J Biol Chem. 2001;276:3963–3970. [PubMed]
69. Ding L, Doñate F, Parry GCN, Guan X, Maher P, Levin E. Inhibition of cell migration and angiogenesis by the amino-terminal fragment of 24kD basic fibroblast growth factor. J Biol Chem. 2002;277:31056–31061. [PubMed]
70. Yu PJ, Ferrari G, Pirelli L, Galloway AC, Mignatti P, Pintucci G. Thrombin cleaves the high molecular weight forms of basic fibroblast growth factor (FGF-2): a novel mechanism for the control of FGF-2 and thrombin activity. Oncogene. 2008;27:2594–2601. [PMC free article] [PubMed]
71. Levin EG, Sikora L, Ding L, Rao SP, Sriramaro P. Suppression of tumor growth and angiogenesis in vivo by a truncated form of 24-kd fibroblast growth factor (FGF)-2. Am J Pathol. 2004;164:1183–1190. [PMC free article] [PubMed]
72. Padua RR, Kardami E. Increased basic fibroblast growth factor (bFGF) accumulation and distinct patterns of localization in isoproterenol-induced cardiomyocyte injury. Growth Factors. 1993;8:291–306. [PubMed]
73. Kardami E, Jiang ZS, Jimenez SK, Hirst CJ, Sheikh F, Zahradka P, Cattini PA. Fibroblast growth factor 2 isoforms and cardiac hyperthrophy. Cardiovascular Res. 2004;63:458–466. [PubMed]
74. Powell PP, Finklestein SP, Dionne CA, Jaye M, Klagsbrun M. Temporal, differential and regional expression of mRNA for basic fibroblast growth factor in the developing and adult rat brain. Brain Res Mol Brain Res. 1991;11:71–77. [PubMed]
75. Timmer M, Müller-Ostermeyer F, Kloth V, Winkler C, Grothe C, Nikkhah G. Enhanced survival, reinnervation, and functional recovery of intrastriatal dopamine grafts co-transplanted with Schwann cells overexpressing high molecular weight FGF-2 isoforms. Exp Neurol. 2004;187:118–136. [PubMed]
76. Grothe C, Schulze A, Semkova I, Müller-Ostermeyer F, Rege A, Wewetzer K. The high molecular weight fibroblast growth factor-2 isoforms (21,000 mol. wt and 23,000 mol wt) mediate neurotrophic activity on rat embryonic mesencephalic dopaminergic neurons in vitro. Neuroscience. 2000;100:73–86. [PubMed]
77. Timmer M, Robben S, Müller-Ostermeyer F, Nikkhah G, Grothe C. Axonal regeneration across long gaps in silicone chambers filled with Schwann cells overexpressing high molecular weight FGF-2. Cell Tansplant. 2003;12:265–277. [PubMed]
78. Haastert K, Lipokatic E, Fischer M, Timmer M, Grothe C. Differentially promoted peripheral nerve regeneration by grafted Schwann cells over-expressing different FGF-2 isoforms. Neurobiol Dis. 2006;21:138–153. [PubMed]
79. Thomas-Mudge RJ, Okada-Ban M, Vandenbroucke F, Vincent-Salomon A, Girault JM, Thiery JP, Jouanneau J. Nuclear FGF-2 facilitates cell survival in vitro during establishment of metastases. Oncogene. 2004;23:4771–4779. [PubMed]
80. ADHR consortium. Autosomal dominant hypophosphataemic rickets is associated with mutations in FGF23. Nat Genet. 2000;26:345–348. [PubMed]
81. Dighiero G, Hamblin TJ. Chronic lymphoid leukaemia. Lancet. 2008;371:1017–1029. [PubMed]
82. Krejci P, Dvorakova D, Krahulcova E, Pachernik J, Mayer J, Hampl A, Dvorak P. FGF-2 abnormalities in B cell chronic lymphocytic and chronic myeloid leukemias. Leukemia. 2001;15:228–237. [PubMed]
83. Krejci P, Pejchalova K, Rosenbloom BE, Rosenfelt FP, Tran EL, Laurell H, Wilcox WR. The antiapoptotic protein Api5 and its partner, high molecular weight FGF-2, are up-regulated in B cell chronic lymphoid leukemia. J Leu Biol. 2007;82:1363–1364. [PubMed]
84. Menzel T, Rahman Z, Calleja E, White K, Wilson EL, Wieder R, Gabrilove J. Elevated intracellular level of basic fibroblast growth factor correlates with stage of chronic lymphocytic leukemia and is associated with resistance to fludarabine. Blood. 1996;87:1056–1063. [PubMed]
85. Gaubert F, Escaffit F, Bertrand C, Korc M, Pradayrol L, Clemente F, Estival A. Expression of the high molecular weight fibroblast growth factor-2 isoform of 210 amino acids is associated with modulation of protein kinases C delta and epsilon and ERK activation. J Biol Chem. 2001;276:1545–1554. [PubMed]
86. Quarto N, Fong KD, Longaker MT. Gene profiling of cells expressing different FGF-2 forms. Gene. 2005;356:49–68. [PubMed]
87. Tewari M, Yu M, Ross B, Dean C, Giordano A, Rubin R. AAC-11, a novel cDNA that inhibits apoptosis after growth factor withdrawal. Cancer Res. 1997;57:4063–4069. [PubMed]
88. Kim JW, Cho HS, Kim JH, Hur SY, Kim TE, Lee JM, Kim IK, Namkoong SE. AAC-11 over-expression induces invasion and protects cervical cancer cells from apoptosis. Lab Invest. 2000;80:587–594. [PubMed]
89. Van den Berghe L, Laurell H, Huez I, Zanibellato C, Prats H, Bugler B. FIF [fibroblast growth factor-2 (FGF-2)-interacting-factor], a nuclear putatively antiapoptotic factor, interacts specifically with FGF-2. Mol Endocrinol. 2000;14:1709–1724. [PubMed]
90. Klein S, Morimoto T, Rifkin DB. Characterisation of fibroblast growth factor-2 binding to ribosomes. Growth Factors. 1996;13:219–228. [PubMed]
91. Shen B, Arese M, Gualandris A, Rifkin DB. Intracellular association of FGF-2 with the ribosomal protein L6/TAXREB107. Biochem Biophys Res Commun. 1998;252:524–528. [PubMed]
92. Gringel S, van Bergeijk J, Haastert K, Grothe C, Claus P. Nuclear fibroblast growth factor-2 interacts specifically with splicing factor SF3a66. Biol Chem. 2004;385:1203–1208. [PubMed]
93. Kolb SJ, Battle DJ, Dreyfuss G. Molecular functions of the SMN complex. J Child Neurol. 2007;22:990–994. [PubMed]
94. Lefebvre S, Bürglen L, Reboullet S, Clermont O, Burlet P, Viollet L, Benichou B, Cruaud C, Millasseau P, Zeviani M, Le Paslier D, Frézal J, Cohen D, Weissenbach J, Munnich A, Melki J. Identification and characterization of a spinal muscular atrophy-determining gene. Cell. 1995;80:155–165. [PubMed]
95. Claus P, Bruns AF, Grothe C. Fibroblast growth factor-223 binds directly to the survival of motoneuron protein and is associated with small nuclear RNAs. Biochem J. 2004;384:559–565. [PMC free article] [PubMed]
96. Dvorak P, Dvorakova D, Hampl A. Fibroblast growth factor signalling in embryonic and cancer stem cells. FEBS Lett. 2006;580:2869–2874. [PubMed]
97. Hortala M, Ferjoux G, Estival A, Bertrand C, Schulz S, Pradayrol L, Susini C, Clemente F. Inhibitory role of the somatostatin receptor SST2 on the intracrine-regulated cell proliferation induced by the 210-amino acid fibroblast growth factor-2 isoform implication of JAK2. J Biol Chem. 2003;278:20574–20581. [PubMed]
98. Korah RM, Sysounthone V, Golowa Y, Wieder R. Basic fibroblast growth factor confers a less malignant phenotype in MDA-MB-231 human breast cancer cells. Cancer Research. 2000;60:733–740. [PubMed]
99. Ma X, Dang X, Claus P, Hirst C, Fandrich RR, Jin Y, Grothe C, Kirshenbaum LA, Cattini PA, Kardami E. Chromatin compaction and cell death by high molecular weight FGF2 depend on its nuclear localization, intracrine ERK activation, and engagement of mitochondria. J Cell Physiol. 2007;213:690–698. [PubMed]
100. Nindl W, Kavakebi P, Claus P, Grothe C, Pfaller K, Klimaschewski L. Expression of basic fibroblast growth factor isoforms in postmitotic sympathetic neurons: synthesis, intracellular localization and involvement in karyokinesis. Neuroscience. 2004;124:561–572. [PubMed]
101. Okada-Ban M, Moens G, Thiery JP, Jouanneau J. Nuclear 24 kD fibroblast growth factor (FGF)-2 confers metastatic properties on rat bladder carcinoma cells. Oncogene. 1999;18:6719–6724. [PubMed]
102. Piotrowicz RS, Maher PA, Levin EG. Dual activities of 22–24 kDa basic fibroblast growth factor: Inhibition of migration and stimulation of proliferation. J Cell Physiol. 1999;178:144–153. [PubMed]
103. Quarto N, Talarico D, Florkiewicz R, Rifkin DB. Selective expression of high molecular weight basic fibroblast growth factor confers a unique phenotype to NIH 3T3 cells. Cell Regulation. 1991;2:699–708. [PMC free article] [PubMed]
104. Hirst CJ, Herlyn M, Cattini PA, Kardami E. High levels of CUG-initiated FGF-2 expression cause chromatic compaction, decreased cardiomyocyte mitosis, and cell death. Mol Cell Biochem. 2003;246:111–116. [PubMed]
PubReader format: click here to try


Related citations in PubMed

See reviews...See all...

Cited by other articles in PMC

See all...


  • MedGen
    Related information in MedGen
  • PubMed
    PubMed citations for these articles
  • Substance
    PubChem Substance links

Recent Activity

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

See more...