• We are sorry, but NCBI web applications do not support your browser and may not function properly. More information
Logo of embojLink to Publisher's site
EMBO J. Mar 1989; 8(3): 681–686.
PMCID: PMC400861

Regulation of the mannose 6-phosphate/IGF II receptor expression at the cell surface by mannose 6-phosphate, insulin like growth factors and epidermal growth factor.


Mannose 6-phosphate, insulin like growth factors I and II (IGF I, IGF II), insulin and epidermal growth factor (EGF) induce a 1.5- to 2-fold increase of mannose 6-phosphate binding sites at the cell surface of human skin fibroblasts. The increase is completed within 10-15 min, is dose and temperature dependent, reversible and transient even in the presence of the effectors. It is due to a redistribution of mannose 6-phosphate/IGF II receptors from internal membranes to the cell surface, while the affinity of the receptors is not affected. Combinations of mannose 6-phosphate with IGF I, IGF II or EGF stimulate the redistribution of the receptor to the cell surface in an additive manner, while combinations of the growth factors result in a non-additive stimulation of redistribution. The redistribution is not dependent on extracellular calcium and appears also to be independent of changes of free intracellular calcium. Pre-treatment of fibroblasts with cholera toxin or pertussis toxin increases the number of cell surface receptors 2- and 1.5-fold, respectively. Neither of the toxins affects the redistribution of mannose 6-phosphate/IGF II receptors induced by the growth factors, while both toxins abolish the receptor redistribution induced by mannose 6-phosphate. These results suggest a multiple regulation of the cell surface expression of mannose 6-phosphate/IGF II receptors by Gs- and Gi-like proteins sensitive to cholera toxin and pertussis toxin and by stimulation of mannose 6-phosphate/IGF II, IGF I and EGF receptors.(ABSTRACT TRUNCATED AT 250 WORDS)

Full text

Full text is available as a scanned copy of the original print version. Get a printable copy (PDF file) of the complete article (1.1M), or click on a page image below to browse page by page. Links to PubMed are also available for Selected References.

Selected References

These references are in PubMed. This may not be the complete list of references from this article.
  • Corvera S, Folander K, Clairmont KB, Czech MP. A highly phosphorylated subpopulation of insulin-like growth factor II/mannose 6-phosphate receptors is concentrated in a clathrin-enriched plasma membrane fraction. Proc Natl Acad Sci U S A. 1988 Oct;85(20):7567–7571. [PMC free article] [PubMed]
  • Fischer HD, Gonzalez-Noriega A, Sly WS. Beta-glucuronidase binding to human fibroblast membrane receptors. J Biol Chem. 1980 Jun 10;255(11):5069–5074. [PubMed]
  • Gelfand EW, Mills GB, Cheung RK, Lee JW, Grinstein S. Transmembrane ion fluxes during activation of human T lymphocytes: role of Ca2+, Na+/H+ exchange and phospholipid turnover. Immunol Rev. 1987 Feb;95:59–87. [PubMed]
  • Gilman AG. G proteins: transducers of receptor-generated signals. Annu Rev Biochem. 1987;56:615–649. [PubMed]
  • Grynkiewicz G, Poenie M, Tsien RY. A new generation of Ca2+ indicators with greatly improved fluorescence properties. J Biol Chem. 1985 Mar 25;260(6):3440–3450. [PubMed]
  • Hari J, Pierce SB, Morgan DO, Sara V, Smith MC, Roth RA. The receptor for insulin-like growth factor II mediates an insulin-like response. EMBO J. 1987 Nov;6(11):3367–3371. [PMC free article] [PubMed]
  • Kaplan A, Achord DT, Sly WS. Phosphohexosyl components of a lysosomal enzyme are recognized by pinocytosis receptors on human fibroblasts. Proc Natl Acad Sci U S A. 1977 May;74(5):2026–2030. [PMC free article] [PubMed]
  • Kiess W, Blickenstaff GD, Sklar MM, Thomas CL, Nissley SP, Sahagian GG. Biochemical evidence that the type II insulin-like growth factor receptor is identical to the cation-independent mannose 6-phosphate receptor. J Biol Chem. 1988 Jul 5;263(19):9339–9344. [PubMed]
  • LOWRY OH, ROSEBROUGH NJ, FARR AL, RANDALL RJ. Protein measurement with the Folin phenol reagent. J Biol Chem. 1951 Nov;193(1):265–275. [PubMed]
  • MacDonald RG, Pfeffer SR, Coussens L, Tepper MA, Brocklebank CM, Mole JE, Anderson JK, Chen E, Czech MP, Ullrich A. A single receptor binds both insulin-like growth factor II and mannose-6-phosphate. Science. 1988 Mar 4;239(4844):1134–1137. [PubMed]
  • Maly P, Lüthi C. Characterization of affinity-purified type I insulin-like growth factor receptor from human placenta. Biochem Biophys Res Commun. 1986 Aug 14;138(3):1257–1262. [PubMed]
  • Mellas J, Gavin JR, 3rd, Hammerman MR. Multiplication-stimulating activity-induced alkalinization of canine renal proximal tubular cells. J Biol Chem. 1986 Nov 5;261(31):14437–14442. [PubMed]
  • Morgan DO, Edman JC, Standring DN, Fried VA, Smith MC, Roth RA, Rutter WJ. Insulin-like growth factor II receptor as a multifunctional binding protein. Nature. 1987 Sep 24;329(6137):301–307. [PubMed]
  • Neer EJ, Clapham DE. Roles of G protein subunits in transmembrane signalling. Nature. 1988 May 12;333(6169):129–134. [PubMed]
  • Neher E. The influence of intracellular calcium concentration on degranulation of dialysed mast cells from rat peritoneum. J Physiol. 1988 Jan;395:193–214. [PMC free article] [PubMed]
  • Nishimoto I, Hata Y, Ogata E, Kojima I. Insulin-like growth factor II stimulates calcium influx in competent BALB/c 3T3 cells primed with epidermal growth factor. Characteristics of calcium influx and involvement of GTP-binding protein. J Biol Chem. 1987 Sep 5;262(25):12120–12126. [PubMed]
  • Oka Y, Czech MP. The type II insulin-like growth factor receptor is internalized and recycles in the absence of ligand. J Biol Chem. 1986 Jul 15;261(20):9090–9093. [PubMed]
  • Oka Y, Mottola C, Oppenheimer CL, Czech MP. Insulin activates the appearance of insulin-like growth factor II receptors on the adipocyte cell surface. Proc Natl Acad Sci U S A. 1984 Jul;81(13):4028–4032. [PMC free article] [PubMed]
  • Rechler MM, Nissley SP. The nature and regulation of the receptors for insulin-like growth factors. Annu Rev Physiol. 1985;47:425–442. [PubMed]
  • Rogers SA, Hammerman MR. Insulin-like growth factor II stimulates production of inositol trisphosphate in proximal tubular basolateral membranes from canine kidney. Proc Natl Acad Sci U S A. 1988 Jun;85(11):4037–4041. [PMC free article] [PubMed]
  • Roth RA. Structure of the receptor for insulin-like growth factor II: the puzzle amplified. Science. 1988 Mar 11;239(4845):1269–1271. [PubMed]
  • Roth RA, Stover C, Hari J, Morgan DO, Smith MC, Sara V, Fried VA. Interactions of the receptor for insulin-like growth factor II with mannose-6-phosphate and antibodies to the mannose-6-phosphate receptor. Biochem Biophys Res Commun. 1987 Dec 16;149(2):600–606. [PubMed]
  • Sessions CM, Emler CA, Schalch DS. Interaction of insulin-like growth factor II with rat chondrocytes: receptor binding, internalization, and degradation. Endocrinology. 1987 May;120(5):2108–2116. [PubMed]
  • Stein M, Zijderhand-Bleekemolen JE, Geuze H, Hasilik A, von Figura K. Mr 46,000 mannose 6-phosphate specific receptor: its role in targeting of lysosomal enzymes. EMBO J. 1987 Sep;6(9):2677–2681. [PMC free article] [PubMed]
  • Tally M, Enberg G, Li CH, Hall K. The specificity of the human IGF-2 receptor. Biochem Biophys Res Commun. 1987 Sep 30;147(3):1206–1212. [PubMed]
  • Tally M, Li CH, Hall K. IGF-2 stimulated growth mediated by the somatomedin type 2 receptor. Biochem Biophys Res Commun. 1987 Oct 29;148(2):811–816. [PubMed]
  • Tong PY, Tollefsen SE, Kornfeld S. The cation-independent mannose 6-phosphate receptor binds insulin-like growth factor II. J Biol Chem. 1988 Feb 25;263(6):2585–2588. [PubMed]
  • von Figura K, Hasilik A. Lysosomal enzymes and their receptors. Annu Rev Biochem. 1986;55:167–193. [PubMed]
  • Waheed A, Braulke T, Junghans U, von Figura K. Mannose 6-phosphate/insulin like growth factor II receptor: the two types of ligands bind simultaneously to one receptor at different sites. Biochem Biophys Res Commun. 1988 May 16;152(3):1248–1254. [PubMed]
  • Wardzala LJ, Simpson IA, Rechler MM, Cushman SW. Potential mechanism of the stimulatory action of insulin on insulin-like growth factor II binding to the isolated rat adipose cell. Apparent redistribution of receptors cycling between a large intracellular pool and the plasma membrane. J Biol Chem. 1984 Jul 10;259(13):8378–8383. [PubMed]
  • Barenton B, Guyda HJ, Goodyer CG, Polychronakos C, Posner BI. Specificity of insulin-like growth factor binding to type-II IGF receptors in rabbit mammary gland and hypophysectomized rat liver. Biochem Biophys Res Commun. 1987 Dec 16;149(2):555–561. [PubMed]
  • Braulke T, Gartung C, Hasilik A, von Figura K. Is movement of mannose 6-phosphate-specific receptor triggered by binding of lysosomal enzymes? J Cell Biol. 1987 Jun;104(6):1735–1742. [PMC free article] [PubMed]
  • Bretthauer RK, Kaczorowski GJ, Weise MJ. Characterization of a phosphorylated pentasaccharide isolated from Hansenula holstii NRRL Y-2448 phosphomannan. Biochemistry. 1973 Mar 27;12(7):1251–1256. [PubMed]
  • Bryson JM, Baxter RC. High-affinity receptor for insulin-like growth factor II in rat liver: properties and regulation in vivo. J Endocrinol. 1987 Apr;113(1):27–35. [PubMed]
  • Corvera S, Roach PJ, DePaoli-Roach AA, Czech MP. Insulin action inhibits insulin-like growth factor-II (IGF-II) receptor phosphorylation in H-35 hepatoma cells. IGF-II receptors isolated from insulin-treated cells exhibit enhanced in vitro phosphorylation by casein kinase II. J Biol Chem. 1988 Mar 5;263(7):3116–3122. [PubMed]

Articles from The EMBO Journal are provided here courtesy of The European Molecular Biology Organization


Related citations in PubMed

See reviews...See all...

Cited by other articles in PMC

See all...


  • Compound
    PubChem Compound links
  • 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...