NCBI Bookshelf. A service of the National Library of Medicine, National Institutes of Health.

Madame Curie Bioscience Database [Internet]. Austin (TX): Landes Bioscience; 2000-.

Cover of Madame Curie Bioscience Database

Madame Curie Bioscience Database [Internet].

Show details

Gas7

, , , , , and *.

* Corresponding Author: Sue Lin-Chao—Institute of Molecular Biology, Academia Sinica, #128, Sec. 2, Academia Rd, Nankang, Taipei 11529, Taiwan. Email: wt.ude.acinis.etag@eusbm

Gas7 (growth-arrest specific gene 7) has recently been classified to be a member of the Pombe Cdc 15 homology (PCH) family and belongs to the proline, serine, threonine-rich phosphatase interacting protein (PSTPIP) subfamily.1,2 Most PCH proteins share a similar domain architecture, which is composed of an N-terminal Fes/CIP4 homology (FCH) domain, a coiled-coil (CC) region and one or two Src homology (SH3) domains.1 The PSTPIPs, a subfamily of the PCH proteins, are tyrosine-phosphorylated proteins involved in the organization of the cytoskeleton and are substrates for the PEST-type protein tyrosine phosphatases.3,4 Among the PSTPIPs, PSTPIP1 interacts with neural Wiskott-Aldrich Syndrome protein (N-WASP) and the interaction is regulated by phosphorylation on two tyrosine residues in the SH3 domain.5 In addition, another member of the PSTPIP subfamily, PSTPIP2, has been proven to directly bind and crosslink actin to induce filopodia formation.6,7 This chapter will present the identified characteristics of mouse Gas7 as well as its physiological roles in relation to the PCH proteins, especially the PSTPIP family.

Introduction

Growth arrest-specific (gas) genes were originally identified and isolated from cultured cells undergoing serum deprivation or growth to confluence.8,9 Despite their defining feature—being preferentially expressed in G0 phase—gas genes have no sequence similarity and exert disparate functions in either proliferating and/or differentiated cells.10-13 The gas7 gene was first discovered in growth-arrested NIH3T3 fibroblasts by a retrovirus-based gene search strategy9 and is evolutionally conserved in mammals including Equus caballus (horse), Bos Taurus (cattle), Mus musculus (mouse), Rattus norvegicus (rat), Macaca mulatta (rhesus monkey), Pan troglodytes (chimpanzee) and Homo sapiens (http://www.ncbi.nlm.nih.gov/mapview/). Orthologs of gas7 gene have been identified and cloned from mouse, rat and human.12,14-16 Regardless of the species in which each gas7 gene originated, individual gas7 genes encode more than one protein isoform,12,14-16 which are potentially regulated by unknown mechanisms such as alternative RNA splicing, different promoters and/or miRNAs (Fig. 1).

Figure 1. Sequence alignment of Gas7 orthologs.

Figure 1

Sequence alignment of Gas7 orthologs. All sequences are available in the public domain. m, h and r are abbreviations of Mus musculus, Homo sapiens and Rattus norvegicus, respectively. Accession numbers of each sequence are as follows: mGas7 isoform a: (more...)

Following the gradual completion of various genome sequences by the genome projects, chromosomal locations of gas7 gene in different species have been determined and information is available in the public domain. Gas7 gene is recognized as important from a genetic as well as an evolutionary viewpoint because of its high conservation of othologous DNA and protein sequences among various species. Chromosomal mapping has located gas7 gene on human chromosome 17, which is rich in protein-coding genes and has the second highest gene density in the human genome. It is particularly rich in disease genes such as the breast cancer gene BRCA1, the neurofibromatosis gene NF1 and the gene associated with repairing DNA damage TP53.17 In addition, human chromosome 17 shares its roots with a single mouse chromosome, chromosome 11. Conserved synteny extends among human chromosome 17, mouse chromosome 11 and rat chromosome 10 for many genes including gas7.18-20 All research to-date points to the biological significance of Gas7 and hints that it is worthy of more efforts and further investigation.

Properties of Gas7

Physical and Biochemical Properties

Although Gas7 is a new member of PSTPIP family, it has been proven for years to directly interact with actin via its C-terminus and contribute to the formation of membrane protrusions including filopodia and lamellipodia.21 Endogenous Gas7 protein from mouse brain exhibited a molecular weight of around 48 KDa on SDS-PAGE with predicted pI ranging from 7.68 to 6.01 according to its phoshphorylation states (Table 1).22-24 Phosphorylation sites in mouse Gas7 have also been predicated by computational methods.25 Tyrosine residues in the WW or coiled-coil domains and several serine/threonine sites are predicted to be putatively phosphorylated. An important feature of the PSTPIP family proteins is that the status of tyrosine phosphorylation on PSTPIPs regulates the interaction between PSTPIPs and other proteins. For example, tyrosine phosphorylation on the SH3 domain mediates the interaction with the proline-rich domain of WASP; level of tyrosine phosphorylation on the coiled-coil domain affects its association to the plasma membrane and interaction with PEST-type protein-tyrosine phosphatase (PTP-PEST).4,5 The necessity of tyrosine phosphorylation for Gas7 to interact with other proteins, therefore, deserves to be further addressed.

Table 1. Predicted pI and molecular weight of mouse Gas7 protein.

Table 1

Predicted pI and molecular weight of mouse Gas7 protein.

Domain Structure of Gas7 Proteins

Human Gas7 protein isoform c possesses SH3, WW, Fes/CIP4 homology (FCH) and coiled-coil domains in a slightly different orientation from the PCH proteins. Mouse Gas7 protein (i.e., mGas7 isoform a) consists of an N-terminal WW domain, a FCH domain and a C-terminal coiled-coil (CC) region. Despite the sequence similarity among Gas7 orthologs (Fig. 1) (Sequences were aligned by CLUSTALW and presented by TEXSHADE at http://seqtool.sdsc.edu/), only mouse Gas7 isoform a and human Gas7 isoform c possess a domain structure similar to the PCH proteins except for the inclusion of the SH3 domain which is absent from mouse Gas7 (Fig. 2) (Domains were predicted by the ELM server at http://elm.eu.org).

Figure 2. Schematic representation of the domain structures in Gas7 orthologs.

Figure 2

Schematic representation of the domain structures in Gas7 orthologs.

Tissue Distribution and Subcellular Localization of Gas7

Studies have revealed that Gas7 is predominantly expressed in brain tissues including cerebral cortex, hippocampus and cerebellum.12 Tissue distribution of mouse Gas7 has been extensively examined in the laboratory by western blotting and summarized in Table 2. Briefly, Gas7 is abundantly expressed in brain as well as in testis tissue. Low expression of Gas7 is detected in other tissues such as heart, spleen, lung, prostate, ovary and skeletal muscle. Immunohistochemistry and immunofluorescent staining have shown that at the subcellular level Gas7 is mainly distributed in the cytoplasm with preferential localization in the submembrane region.12,21

Table 2. Tissue distribution of Gas7 protein and isoforms.

Table 2

Tissue distribution of Gas7 protein and isoforms.

Gas7 Is Expressed during Embryogenesis

Embryogenesis is a complicated process accomplished by vigorous cell division and differentiation, which orchestrate rearrangements of the cytoskeleton. Involvement of Gas7 in morphological differentiation as well as in neuritogenesis implies that Gas7 is important in cytoskeleton dynamics and led us to examine the expression of Gas7 in embryogenesis. As shown in Figure 3, Gas7 protein was detected by immunochemical technology in mouse embryo from 12.5 days postcoitum (dpc). In the embryo at 12.5 dpc, the heart reveals the strong anti-Gas7 antibody staining while the neuroepithelium shows moderate expression of Gas7 (Fig. 3A, E). Gas7 was not detected in the diaphragm muscle until 14.5 dpc, when a high level of Gas7 expression appeared (Fig. 3C). At 16.5 dpc, Gas7 was highly expressed in the whole liver (Fig. 3G) and pancreas (Fig. 3L). It was also dominantly expressed in the bronchial tree of the embryonic lung (Fig. 3B) as well as in the intestine (Fig. 3K). A weak Gas7 staining pattern or no staining was seen in the epithelial cells of the stomach (Fig. 3J). Embryonic metanephros expressed Gas7 in both excretory tubules and glomeruli (Fig. 3H). In addition, we performed double staining to distinguish the expression of Gas7 from Gas7-cb in the neuroepithelium (Fig. 3E, F) and in adrenal glands (Fig. 3I). Gas7-cb was mainly localized in the nuclei of cells in the developing brain while Gas7 was expressed in the cytoplasm of cells over the whole neuroepithelium, especially in the spinal cord (Fig. 3D). Gas7 was expressed in adrenal glands while Gas7-cb was found in the nuclei of the adrenal medulla (Fig. 3I). In conclusion, Gas7 was expressed at the early differentiation stage in various systems derived from the three germinal layers. Gas7-cb was expressed relatively specifically in the nuclei of cells derived from the neuroepithelium or in neural crest cells. Regional distribution of Gas7 protein in mouse embryo is summarized in Table 3.

Figure 3. Expression of Gas7 in mouse embryo.

Figure 3

Expression of Gas7 in mouse embryo. A) Gas7 was detected in heart at 12.5 days postcoitum (dpc). B) Weak staining of Gas7 was found in the bronchial tree of embryonic lung at 14.5 dpc. C) Strong Gas7 expression in diaphragm. D) Strong cytoplasmic Gas7 (more...)

Table 3. Regional distribution of Gas7 protein in mice embryos.

Table 3

Regional distribution of Gas7 protein in mice embryos.

Physiological Functions of Gas7

Functional studies of Gas7 protein started from overexpression and antisense RNA inhibition in cultured cells. Overexpression of Gas7 has been carried out in cell lines including Neura-2A, PC12 and NIH3T3 cells.12,21,26 Antisense RNA inhibition of Gas7 expression was performed in PC12 cells and primary neuronal culture of cerebellum.12,26 Form these studies, Gas7 has been proven to directly interact with actin and is implicated to be functionally involved in morphological differentiation as well as in neuritogenesis. Recent work done by Chang et al also provides a functional link between Gas7 and chondrogenesis.27

Direct Interaction of Gas7 and Actin Promotes Formation of Membrane Protrusions

Gas7 was proven to directly interact with actin in 2002 by She et al. Endogenous Gas7 expression is induced significantly in NIH3T3 cells upon serum starvation and remains elevated above the basal level during the initiating period as the cells are released from growth arrest. The short and specific time window for Gas7 expression allowed the observation of endogenous Gas7 localization. It was the first time that Gas7 was observed to be enriched and colocalized with actin microfilaments in regions near the plasma membrane and structures that appeared in response to serum stimulation such as membrane ruffles, lamellipodia and filopodia. This finding was further confirmed by ectopic expression of Gas7 in NIH3T3 cells. Overexpression of Gas7 caused NIH3T3 cells to undergo extensive morphological change—forming extensive cellular processes. This action was later shown to be disrupted by cytochalasin D and led to the conclusion that Gas7-induced morphological change is a consequence of actin microfilament rearrangement.

As early as 2002, She et al noted that the C-terminal region of Gas7 was very similar to the microfilament-localization domain, which was characterized in PSTPIP3,5 and is now defined as the F-BAR domain. After a series of experiments, Gas7 was concluded to be associated with actin microfilaments directly through its C-terminal domain. Neither the N- nor the C-terminal region alone, however, was concluded sufficient to induce the morphological changes that were observed following over-expression of full-length Gas7.21

Inhibition of Gas7 Expression by Antisense Oligonucleotide Impedes Neurite Formation

Antisense inhibition of gas7 expression by gas7-specific antisense oligonucleotides was first applied to primary cerebellar neuronal culture from mouse brain. It was found that specific inhibition of Gas7 protein is associated with an overall reduction in neurite formation of gas7-expressing cells.12 The effect of Gas7 protein in neurite formation was later confirmed in PC12 cells, which were originated from rat pheochromocytoma and maintained in a preneuronal state in the absence of Nerve Growth Factor (NGF). Upon NGF treatment, PC12 cells underwent morphological changes, began to differentiate and formed neurites with tyrosine hydroxylase, one of the neuronal differentiation markers.28 Upon treatment with gas7-specific antisense oligonucleotide prior to NGF induction, PC12 cells exhibited a significant decrease in NGF-induced neurite formation.26 To date, it is not understood how Gas7 functionally affects neuritogenesis.

Ectopic Expression of Gas7 Induces Morphological Differentiation

Overexpression of Gas7 in mouse neuroblastoma Neura2A cells causes a dramatic morphological change and production of neurite-like extensions lack of detectable neuronal differentiation marker.12 Over-expression of Gas7 also promotes the outgrowth of NGF-induced neurites in preneuronal PC12 cells.26 Many PCH proteins have been demonstrated to interact with membrane phospholipids via the F-BAR domain. This interaction renders the PCH proteins to coordinate actin cytoskeleton and membrane deformation, which results in membrane tabulation.1,2,29,30 The F-BAR domain of Gas7 may thus potentially function to interact with membrane phospholipids and participate in actin cytoskeletal reorganization that leads to the formation of membrane protrusions.

In addition to the F-BAR domain, the WW domain of Gas7 may also function to regulate actin dynamics. The WASP family proteins are well-known for their regulatory effect on actin dynamics, which is essential for a variety of cellular processes such as formation of membrane protrusions. Besides, the WASP family proteins are regarded as important interacting factors for the PCH family proteins including CIP4a, FBP17, Toca-1, NOSTRIN, PSTPIP1, Syndapsins and PACSINs.2,5,6,31-40 Most of the interactions between PCH proteins and WASP family members are mediated by direct binding of the SH3 domain (from PCH) to the Proline-rich region (from WASP). The molecular and functional convergence between WW and SH3 domains has been explored and it has been reported that the binding surface of the modeled WW domain reveals high similarities to the SH3 domain and may bind specifically to the Proline-rich region.41 Gas7 protein thus may interact with the WASP family proteins via its WW domain to participate in the coordination of cytoskeleton reorganization.

Gas7 Proteins in Chondrogenesis

Bone marrow derived mesenchymal stem cells, which possess the pluripotency to differentiate into distinct cell lineages, have been widely applied in studies on tissue engineering and regenerative medicine such as chondrogenesis. A recent study by Chang et al, using human bone marrow derived mesenchymal stem cells (hMSCs) found that human Gas7 isoform b (hGas7-b) is transiently expressed in transforming growth factor-beta (TGFβ)-induced chondrogenesis. Overexpression of hGas7-b can neither induce nor further promote chondrogenesis of hMSCs irrespective of the presence or absence of TGFβ; however, interruption of hGas7-b expression by specific antisense oligonucleotides impedes the TGFβ-induced chondrogenesis of hMSCs to a similar extent that caused by blocking ERK1/2-SOX9 signaling.27,42-44 This indicates that the expression of hGas7-b may not be sufficient to induce/promote chondrogenesis, but its transient expression is essential for chondrogenesis. Its molecular machinery and signaling cascades; however, remain to be clarified.

Gas7 Protein in Disease

Involvement of Gas7 in disease was firstnoted in a study of experimental autoimmune encephalomyelitis (EAE). Paglinawan et al applied microarray technology to examine genes that were affected by TGFβ to help the recovery from EAE. Gas7 was found and categorized among genes mediating cell migration that were directly inhibited by TGFβ. This suggests that Gas7 protein may be functionally involved in chemokine-induced migration in the immune system.45 Another PSTPIP family member, PSTPIP1, was reported to regulate actin organization at the immunological synapse and affect T-cell activation.32 A multi-tissue expression pattern of Gas7 protein revealed that Gas7 is also expressed in the spleen, though at a low level. This raises the possibility that Gas7 might participate in lymphocyte physiology, which is directed by its actin reorganization ability.

Involvement of the Gas7 protein in malignant transformation was suggested by the occurrence of Gas7 as a fusion partner with MLL (myeloid/lymphoid or mixed-lineage leukemia) in the treatment-related acute myeloid leukemia.46 MLL is a histone methyltransferase and its chromosomal rearrangements are associated with a variety of primary and secondary acute leukemias in children and adults.47-49 It is known to fuse with up to 50 different partner proteins, which are either nuclear or cytoplasmic in origin and are activated for their oncogenic potential by multiple molecular mechanisms.50 An animal study conducted by So et al has demonstrated that MLL-Gas7 can transform multipotent hematopoietic progenitors and induce mixed lineage leukemias in mice.51 Furthermore, MLL-Gas7 is proven to become oncogenic when activated by homo-dimerization, which is mainly contributed by the coiled-coil domain derived from the fusion partner, Gas7.52

Recently, in a study of lung squamous cell carcinoma (SCC), Tseng et al proposed a role for Gas7 as tumor suppressor gene (TSG). A high fractional allelic loss (FAL) is a common feature of lung SCC; determination of the minimal deletion regions (MDRs) by chromosomal deletion analysis thus facilitates the identification of potential tumor suppressor genes as well as the establishment of molecular markers for disease classification. Among the identified MDRs, Gas7 was selected from the chromosomal region of 17p13 which contains a known TSG (TP53) and examined for its mRNA level in matched tumor and normal lung tissues. Fewer Gas7 transcripts were detected in 57% of examined tumors and therefore Gas7 was suggested to potentially function as a TSG.53

Summary

Gas7 is a newly characterized PCH proteinwhich is evolutionally conserved in mammals. It was initially isolated from growth-arrested NIH3T3 cells by serum-starvation or growth into confluence. Individual gas7 genes from various species encode several isoforms and are expressed in various organs and tissues, mostly in the brain and testis. Gas7 has been found to be required for morphological differentiation and neuritogenesis, which are contributed by the direct interaction of Gas7 with actin and/or plausibly N-WASP to participate in cytoskeleton dynamics and execute different functions in different cellular processes, such as vesicle trafficking, cell migration and/or regulation of differentiation. The importance of Gas7 has also emerged from disease studies in both clinical reports and animal models. Gas7 is now known to be a multi-faceted molecule that acts as an immunomodulator, causes malignant transformation and/or functions as a tumor suppressor gene. The necessity of Gas7 in chondrogenesis also sheds light on the significance of its early expression during embryogenesis.

Acknowledgements

The studies of Gas7 were mainly supported by grants from National Science Council to Dr. Sue Lin-Chao for years. It was also supported by AS-95-TP-B04 and an intramural grant from Academia Sinica. Special thanks go to Miranda Loney for critical reading of the manuscript. We thank the Animal Facility of IMB, Academia Sinica, for animal care; Tzu-Hou Huang and Yung-Fu Lin for technical support in animal breeding and tissue sample preparations.

References

1.
Chitu V, Stanley ER. Pombe Cdc15 homology (PCH) proteins: coordinators of membrane-cytoskeletal interactions. Trends Cell Biol. 2007;17(3):145–156. [PubMed: 17296299]
2.
Tsujita K, Suetsugu S, Sasaki N. et al. Coordination between the actin cytoskeleton and membrane deformation by a novel membrane tubulation domain of PCH proteins is involved in endocytosis. J Cell Biol. 2006;172(2):269–279. [PMC free article: PMC2063556] [PubMed: 16418535]
3.
Spencer S, Dowbenko D, Cheng J. et al. PSTPIP, a tyrosine phosphorylated cleavage furrow-associated protein that is a substrate for a PEST tyrosine phosphatase. J Cell Biol. 1997;138(4):845–860. [PMC free article: PMC2138048] [PubMed: 9265651]
4.
Wu Y, Dowbenko D, Lasky LA. PSTPIP 2, a second tyrosine phosphorylated, cytoskeletal-associated protein that binds a PEST-type protein-tyrosine phosphatase. J Biol Chem. 1998;273(46):30487–30496. [PubMed: 9804817]
5.
Wu Y, Spencer SD, Lasky LA. Tyrosine phosphorylation regulates the SH3-mediated binding of the wiskott-aldrich syndrome protein to PSTPIP, a cytoskeletal-associated protein. J Biol Chem. 1998;273(10):5765–5770. [PubMed: 9488710]
6.
Chitu V, Pixley FJ, Macaluso F. et al. The PCH family member MAYP/PSTPIP2 directly regulates F-actin bundling and enhances filopodia formation and motility in macrophages. Mol Biol Cell. 2005;16(6):2947–2959. [PMC free article: PMC1142438] [PubMed: 15788569]
7.
Yeung YG, Soldera S, Stanley ER. A novel macrophage actin-associated protein (MAYP) is tyrosine-phosphorylated following colony stimulating factor-1 stimulation. J Biol Chem. 1998;273(46):30638–30642. [PubMed: 9804836]
8.
Schneider C, King RM, Philipson L. Genes specifically expressed at growth arrest of mammalian cells. Cell. 1988;54(6):787–793. [PubMed: 3409319]
9.
Brenner DG, Lin-Chao S, Cohen SN. Analysis of mammalian cell genetic regulation in situ by using retrovirus-derived portable exons carrying the escherichia coli lacZ gene. Proc Natl Acad Sci USA. 1989;86(14):5517–5521. [PMC free article: PMC297654] [PubMed: 2501787]
10.
Brancolini C, Edomi P, Marzinotto S. et al. Exposure at the cell surface is required for gas3/PMP22 to regulate both cell death and cell spreading: implication for the charcot-marie-tooth type 1A and dejerine-sottas diseases. Mol Biol Cell. 2000;11(9):2901–2914. [PMC free article: PMC14964] [PubMed: 10982389]
11.
Del Sal G, Ruaro ME, Philipson L. et al. The growth arrest-specific gene, gas1, is involved in growth suppression. Cell. 1992;70(4):595–607. [PubMed: 1505026]
12.
Ju YT, Chang AC, She BR. et al. gas7: A gene expressed preferentially in growth-arrested fibroblasts and terminally differentiated purkinje neurons affects neurite formation. Proc Natl Acad Sci USA. 1998;95(19):11423–11428. [PMC free article: PMC21658] [PubMed: 9736752]
13.
Shankar SL, O'Guin K, Kim M. et al. Gas6/Axl signaling activates the phosphatidylinositol 3-kinase/Akt1 survival pathway to protect oligodendrocytes from tumor necrosis factor alpha-induced apoptosis. J Neurosci. 2006;26(21):5638–5648. [PubMed: 16723520]
14.
Chang PY, Kuo JT, Lin-Chao S. et al. Identification of rat Gas7 isoforms differentially expressed in brain and regulated following kainate-induced neuronal injury. J Neurosci Res. 2005;79(6):788–797. [PubMed: 15657892]
15.
Chao CC, Chang PY, Lu HH. Human Gas7 isoforms homologous to mouse transcripts differentially induce neurite outgrowth. J Neurosci Res. 2005;81(2):153–162. [PubMed: 15948147]
16.
Lazakovitch EM, She BR, Lien CL. et al. The Gas7 gene encodes two protein isoforms differentially expressed within the brain. Genomics. 1999;61(3):298–306. [PubMed: 10552931]
17.
Zody MC, Garber M, Adams DJ. et al. DNA sequence of human chromosome 17 and analysis of rearrangement in the human lineage. Nature. 2006;440(7087):1045–1049. [PMC free article: PMC2610434] [PubMed: 16625196]
18.
Buchberg AM, Brownell E, Nagata S. et al. A comprehensive genetic map of murine chromosome 11 reveals extensive linkage conservation between mouse and human. Genetics. 1989;122(1):153–161. [PMC free article: PMC1203679] [PubMed: 2567264]
19.
Yeung RS, Buetow KH, Scherpbier-Heddema T. et al. A genetic, physical and comparative map of rat chromosome 10. Mamm Genome. 1996;7(6):425–428. [PubMed: 8662224]
20.
Zimdahl H, Kreitler T, Gosele C. et al. Conserved synteny in rat and mouse for a blood pressure QTL on human chromosome 17. Hypertension. 2002;39(6):1050–1052. [PubMed: 12052840]
21.
She BR, Liou GG, Lin-Chao S. Association of the growth-arrest-specific protein Gas7 with F-actin induces reorganization of microfilaments and promotes membrane outgrowth. Exp Cell Res. 2002;273(1):34–44. [PubMed: 11795944]
22.
Bjellqvist B, Hughes GJ, Pasquali C. et al. The focusing positions of polypeptides in immobilized pH gradients can be predicted from their amino acid sequences. Electrophoresis. 1993;14(10):1023–1031. [PubMed: 8125050]
23.
Gasteiger E, Hoogland C, Gattiker A. et al. Protein identification and analysis tools on the ExPASy Server. The ExPASy Server. 2005:571–607.
24.
Walker JM. The Proteomics protocols handbook. Humana Press. 2005:571–607.
25.
Blom N, Sicheritz-Ponten T, Gupta R. et al. Prediction of posttranslational glycosylation and phosphorylation of proteins from the amino acid sequence. Proteomics. 2004;4(6):1633–1649. [PubMed: 15174133]
26.
Chao CC, Su LJ, Sun NK. et al. Involvement of Gas7 in nerve growth factor-independent and dependent cell processes in PC12 cells. J Neurosci Res. 2003;74(2):248–254. [PubMed: 14515354]
27.
Chang Y, Ueng SWN, Lin-Chao S. et al. Involvement of gas7 along the ERK 1/2 MAP kinase and SOX9 pathway in chondrogenesis of human marrow derived mesenchymal stem cells. Osteoarthritis Cartilage (conditionally accepted) 2008 [PubMed: 18455446]
28.
Greene LA, Tischler AS. Establishment of a noradrenergic clonal line of rat adrenal pheochromocytoma cells which respond to nerve growth factor. Proc Natl Acad Sci USA. 1976;73(7):2424–2428. [PMC free article: PMC430592] [PubMed: 1065897]
29.
Aspenstrom P, Fransson A, Richnau N. Pombe Cdc15 homology proteins: regulators of membrane dynamics and the actin cytoskeleton. Trends Biochem Sci. 2006;31(12):670–679. [PubMed: 17074490]
30.
Itoh T, Erdmann KS, Roux A. et al. Dynamin and the actin cytoskeleton cooperatively regulate plasma membrane invagination by BAR and F-BAR proteins. Dev Cell. 2005;9(6):791–804. [PubMed: 16326391]
31.
Badour K, Zhang J, Shi F. et al. Fyn and PTP-PEST-mediated regulation of wiskott-aldrich syndrome protein (WASp) tyrosine phosphorylation is required for coupling T-cell antigen receptor engagement to WASp effector function and T-cell activation. J Exp Med. 2004;199(1):99–112. [PMC free article: PMC1887720] [PubMed: 14707117]
32.
Badour K, Zhang J, Shi F. et al. The wiskott-Aldrich syndrome protein acts downstream of CD2 and the CD2AP and PSTPIP1 adaptors to promote formation of the immunological synapse. Immunity. 2003;18(1):141–154. [PubMed: 12530983]
33.
Cote JF, Chung PL, Theberge JF. et al. PSTPIP is a substrate of PTP-PEST and serves as a scaffold guiding PTP-PEST toward a specific dephosphorylation of WASP. J Biol Chem. 2002;277(4):2973–2986. [PubMed: 11711533]
34.
Ho HY, Rohatgi R, Lebensohn AM. et al. Toca-1 mediates Cdc42-dependent actin nucleation by activating the N-WASP-WIP complex. Cell. 2004;118(2):203–216. [PubMed: 15260990]
35.
Icking A, Matt S, Opitz N. et al. NOSTRIN functions as a homotrimeric adaptor protein facilitating internalization of eNOS. J Cell Sci. 2005;118(Pt 21):5059–5069. [PubMed: 16234328]
36.
Kessels MM, Dong J, Leibig W. et al. Complexes of syndapin II with dynamin II promote vesicle formation at the trans-golgi network. J Cell Sci. 2006;119(Pt 8):1504–1516. [PubMed: 16551695]
37.
Kessels MM, Qualmann B. Syndapins integrate N-WASP in receptor-mediated endocytosis. Embo J. 2002;21(22):6083–6094. [PMC free article: PMC137196] [PubMed: 12426380]
38.
Modregger J, DiProspero NA, Charles V. et al. PACSIN 1 interacts with huntingtin and is absent from synaptic varicosities in presymptomatic huntington's disease brains. Hum Mol Genet. 2002;11(21):2547–2558. [PubMed: 12354780]
39.
Modregger J, Ritter B, Witter B. et al. All three PACSIN isoforms bind to endocytic proteins and inhibit endocytosis. J Cell Sci. 2000;113(Pt 24):4511–4521. [PubMed: 11082044]
40.
Tian L, Nelson DL, Stewart DM. Cdc42-interacting protein 4 mediates binding of the wiskott-aldrich syndrome protein to microtubules. J Biol Chem. 2000;275(11):7854–7861. [PubMed: 10713100]
41.
Macias MJ, Wiesner S, Sudol M. WW and SH3 domains, two different scaffolds to recognize proline-rich ligands. FEBS Lett. 2002;513(1):30–37. [PubMed: 11911877]
42.
Murakami S, Kan M, McKeehan WL. et al. Up-regulation of the chondrogenic sox9 gene by fibroblast growth factors is mediated by the mitogen-activated protein kinase pathway. Proc Natl Acad Sci USA. 2000;97(3):1113–1118. [PMC free article: PMC15539] [PubMed: 10655493]
43.
Bobick BE, Kulyk WM. The MEK-ERK signaling pathway is a negative regulator of cartilage-specific gene expression in embryonic limb mesenchyme. J Biol Chem. 2004;279(6):4588–4595. [PubMed: 14617631]
44.
Bobick BE, Kulyk WM. MEK-ERK signaling plays diverse roles in the regulation of facial chondrogenesis. Exp Cell Res. 2006;312(7):1079–1092. [PubMed: 16457813]
45.
Paglinawan R, Malipiero U, Schlapbach R. et al. TGFbeta directs gene expression of activated microglia to an anti-inflammatory phenotype strongly focusing on chemokine genes and cell migratory genes. Glia. 2003;44(3):219–231. [PubMed: 14603463]
46.
Megonigal MD, Cheung NK, Rappaport EF. et al. Detection of leukemia-associated MLL-GAS7 translocation early during chemotherapy with DNA topoisomerase II inhibitors. Proc Natl Acad Sci USA. 2000;97(6):2814–2819. [PMC free article: PMC16012] [PubMed: 10706619]
47.
Djabali M, Selleri L, Parry P. et al. A trithorax-like gene is interrupted by chromosome 11q23 translocations in acute leukaemias. Nat Genet. 1992;2(2):113–118. [PubMed: 1303259]
48.
Gu Y, Nakamura T, Alder H. et al. The t(4; 11) chromosome translocation of human acute leukemias fuses the ALL-1 gene, related to drosophila trithorax, to the AF-4 gene. Cell. 1992;71(4):701–708. [PubMed: 1423625]
49.
Tkachuk DC, Kohler S, Cleary ML. Involvement of a homolog of drosophila trithorax by 11q23 chromosomal translocations in acute leukemias. Cell. 1992;71(4):691–700. [PubMed: 1423624]
50.
Dimartino JF, Cleary ML. Mll rearrangements in haematological malignancies: lessons from clinical and biological studies. Br J Haematol. 1999;106(3):614–626. [PubMed: 10468849]
51.
So CW, Karsunky H, Passegue E. et al. MLL-GAS7 transforms multipotent hematopoietic progenitors and induces mixed lineage leukemias in mice. Cancer Cell. 2003;3(2):161–171. [PubMed: 12620410]
52.
So CW, Lin M, Ayton PM. et al. Dimerization contributes to oncogenic activation of MLL chimeras in acute leukemias. Cancer Cell. 2003;4(2):99–110. [PubMed: 12957285]
53.
Tseng RC, Hsieh FJ, Hsu HS. et al. Minimal deletion regions in lung squamous cell carcinoma: Association with abnormality of the DNA double-strand break repair genes and their applications on gene identification and prognostic biomarkers. Lung Cancer. 2007;59(3):332–339. [PubMed: 17931740]
Copyright © 2000-2013, Landes Bioscience.
Bookshelf ID: NBK5988
PubReader format: click here to try

Views

Related information

  • PMC
    PubMed Central citations
  • PubMed
    Links to pubmed

Recent Activity

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

See more...