Skip to main content
NCBI home page
The Journal of Cell Biology logoLink to The Journal of Cell Biology
. 1996 Feb 2;132(4):741–752. doi: 10.1083/jcb.132.4.741

Stimulation of beta1 integrins on fibroblasts induces PDGF independent tyrosine phosphorylation of PDGF beta-receptors

PMCID: PMC2199872  PMID: 8647902

Abstract

We report that integrin-mediated signaling induces a rapid and transient tyrosine phosphorylation of platelet-derived growth factor (PDGF) beta-receptors in human diploid foreskin AG 1518 fibroblasts. A transient tyrosine phosphorylation of PDGF beta-receptors was evident one and two hours after cells had been plated on collagen type I and fibronectin, as well as on immobilized anti-integrin subunit IgG, but not on poly-L-lysine. In contrast EGF or PDGF alpha-receptors were not phosphorylated on tyrosine residues under these conditions. Tyrosine phosphorylation of PDGF beta-receptors induced by plating on collagen type I was inhibited by cytochalasin D and herbimycin A, unaffected by cycloheximide and enhanced by orthovanadate. Furthermore, a transient phosphorylation of PDGF beta-receptors occurred when AG 518 fibroblasts were cultured in three-dimensional collagen lattices or exposed to external strain exerted through centrifugation. The latter effect was evident already after two minutes. Clustering of cell surface beta1 integrins led to PDGF beta-receptor phosphorylation both in suspended and firmly attached AG 1518 fibroblasts. Plating of cells on collagen type I, fibronectin, and anti-beta1-integrin IgG resulted in the formation of PDGF beta-receptor aggregates as detected by immunofluorescence. Suramin or anti-PDGF-BB IgG had no effect on the plating-induced tyrosine phosphorylation of PDGF beta-receptors. PDGF-B chain mRNA, or protein, were not detected in AG 1518 fibroblasts. Our data suggest that a ligand-independent PDGF beta-receptor activation during cell adhesion and early phases of cell spreading is involved in integrin-mediated signaling in fibroblasts, and constitutes parts of a mechanism for cells to respond during the dynamic phases of externally applied tension as well as fibroblast-mediated tension during cell adhesion and collagen gel contraction.

Full Text

The Full Text of this article is available as a PDF (2.9 MB).

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Ahlén K., Rubin K. Platelet-derived growth factor-BB stimulates synthesis of the integrin alpha 2-subunit in human diploid fibroblasts. Exp Cell Res. 1994 Dec;215(2):347–353. doi: 10.1006/excr.1994.1351. [DOI] [PubMed] [Google Scholar]
  2. Albelda S. M., Buck C. A. Integrins and other cell adhesion molecules. FASEB J. 1990 Aug;4(11):2868–2880. [PubMed] [Google Scholar]
  3. Batzer A. G., Rotin D., Ureña J. M., Skolnik E. Y., Schlessinger J. Hierarchy of binding sites for Grb2 and Shc on the epidermal growth factor receptor. Mol Cell Biol. 1994 Aug;14(8):5192–5201. doi: 10.1128/mcb.14.8.5192. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Bell E., Ivarsson B., Merrill C. Production of a tissue-like structure by contraction of collagen lattices by human fibroblasts of different proliferative potential in vitro. Proc Natl Acad Sci U S A. 1979 Mar;76(3):1274–1278. doi: 10.1073/pnas.76.3.1274. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Betsholtz C., Johnsson A., Heldin C. H., Westermark B. Efficient reversion of simian sarcoma virus-transformation and inhibition of growth factor-induced mitogenesis by suramin. Proc Natl Acad Sci U S A. 1986 Sep;83(17):6440–6444. doi: 10.1073/pnas.83.17.6440. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Bissell M. J., Hall H. G., Parry G. How does the extracellular matrix direct gene expression? J Theor Biol. 1982 Nov 7;99(1):31–68. doi: 10.1016/0022-5193(82)90388-5. [DOI] [PubMed] [Google Scholar]
  7. Bornfeldt K. E., Raines E. W., Nakano T., Graves L. M., Krebs E. G., Ross R. Insulin-like growth factor-I and platelet-derived growth factor-BB induce directed migration of human arterial smooth muscle cells via signaling pathways that are distinct from those of proliferation. J Clin Invest. 1994 Mar;93(3):1266–1274. doi: 10.1172/JCI117081. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Burridge K., Fath K., Kelly T., Nuckolls G., Turner C. Focal adhesions: transmembrane junctions between the extracellular matrix and the cytoskeleton. Annu Rev Cell Biol. 1988;4:487–525. doi: 10.1146/annurev.cb.04.110188.002415. [DOI] [PubMed] [Google Scholar]
  9. Burridge K., Turner C. E., Romer L. H. Tyrosine phosphorylation of paxillin and pp125FAK accompanies cell adhesion to extracellular matrix: a role in cytoskeletal assembly. J Cell Biol. 1992 Nov;119(4):893–903. doi: 10.1083/jcb.119.4.893. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Carter W. G., Wayner E. A., Bouchard T. S., Kaur P. The role of integrins alpha 2 beta 1 and alpha 3 beta 1 in cell-cell and cell-substrate adhesion of human epidermal cells. J Cell Biol. 1990 Apr;110(4):1387–1404. doi: 10.1083/jcb.110.4.1387. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Claesson-Welsh L., Eriksson A., Morén A., Severinsson L., Ek B., Ostman A., Betsholtz C., Heldin C. H. cDNA cloning and expression of a human platelet-derived growth factor (PDGF) receptor specific for B-chain-containing PDGF molecules. Mol Cell Biol. 1988 Aug;8(8):3476–3486. doi: 10.1128/mcb.8.8.3476. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Claesson-Welsh L. Platelet-derived growth factor receptor signals. J Biol Chem. 1994 Dec 23;269(51):32023–32026. [PubMed] [Google Scholar]
  13. Clark E. A., Brugge J. S. Integrins and signal transduction pathways: the road taken. Science. 1995 Apr 14;268(5208):233–239. doi: 10.1126/science.7716514. [DOI] [PubMed] [Google Scholar]
  14. Clark R. A., Folkvord J. M., Hart C. E., Murray M. J., McPherson J. M. Platelet isoforms of platelet-derived growth factor stimulate fibroblasts to contract collagen matrices. J Clin Invest. 1989 Sep;84(3):1036–1040. doi: 10.1172/JCI114227. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Cohen B., Yoakim M., Piwnica-Worms H., Roberts T. M., Schaffhausen B. S. Tyrosine phosphorylation is a signal for the trafficking of pp85, an 85-kDa phosphorylated polypeptide associated with phosphatidylinositol kinase activity. Proc Natl Acad Sci U S A. 1990 Jun;87(12):4458–4462. doi: 10.1073/pnas.87.12.4458. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Damsky C. H., Werb Z. Signal transduction by integrin receptors for extracellular matrix: cooperative processing of extracellular information. Curr Opin Cell Biol. 1992 Oct;4(5):772–781. doi: 10.1016/0955-0674(92)90100-q. [DOI] [PubMed] [Google Scholar]
  17. Eriksson A., Siegbahn A., Westermark B., Heldin C. H., Claesson-Welsh L. PDGF alpha- and beta-receptors activate unique and common signal transduction pathways. EMBO J. 1992 Feb;11(2):543–550. doi: 10.1002/j.1460-2075.1992.tb05085.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Fukami K., Endo T., Imamura M., Takenawa T. alpha-Actinin and vinculin are PIP2-binding proteins involved in signaling by tyrosine kinase. J Biol Chem. 1994 Jan 14;269(2):1518–1522. [PubMed] [Google Scholar]
  19. Ginsberg M. H., Du X., Plow E. F. Inside-out integrin signalling. Curr Opin Cell Biol. 1992 Oct;4(5):766–771. doi: 10.1016/0955-0674(92)90099-x. [DOI] [PubMed] [Google Scholar]
  20. Glenney J. R., Jr, Zokas L., Kamps M. P. Monoclonal antibodies to phosphotyrosine. J Immunol Methods. 1988 May 9;109(2):277–285. doi: 10.1016/0022-1759(88)90253-0. [DOI] [PubMed] [Google Scholar]
  21. Guan J. L., Shalloway D. Regulation of focal adhesion-associated protein tyrosine kinase by both cellular adhesion and oncogenic transformation. Nature. 1992 Aug 20;358(6388):690–692. doi: 10.1038/358690a0. [DOI] [PubMed] [Google Scholar]
  22. Guidry C., Grinnell F. Studies on the mechanism of hydrated collagen gel reorganization by human skin fibroblasts. J Cell Sci. 1985 Nov;79:67–81. doi: 10.1242/jcs.79.1.67. [DOI] [PubMed] [Google Scholar]
  23. Gullberg D., Terracio L., Borg T. K., Rubin K. Identification of integrin-like matrix receptors with affinity for interstitial collagens. J Biol Chem. 1989 Jul 25;264(21):12686–12694. [PubMed] [Google Scholar]
  24. Gullberg D., Tingström A., Thuresson A. C., Olsson L., Terracio L., Borg T. K., Rubin K. Beta 1 integrin-mediated collagen gel contraction is stimulated by PDGF. Exp Cell Res. 1990 Feb;186(2):264–272. doi: 10.1016/0014-4827(90)90305-t. [DOI] [PubMed] [Google Scholar]
  25. Hanks S. K., Calalb M. B., Harper M. C., Patel S. K. Focal adhesion protein-tyrosine kinase phosphorylated in response to cell attachment to fibronectin. Proc Natl Acad Sci U S A. 1992 Sep 15;89(18):8487–8491. doi: 10.1073/pnas.89.18.8487. [DOI] [PMC free article] [PubMed] [Google Scholar]
  26. Harris A. K., Stopak D., Wild P. Fibroblast traction as a mechanism for collagen morphogenesis. Nature. 1981 Mar 19;290(5803):249–251. doi: 10.1038/290249a0. [DOI] [PubMed] [Google Scholar]
  27. Hart C. E., Seifert R. A., Ross R., Bowen-Pope D. F. Synthesis, phosphorylation, and degradation of multiple forms of the platelet-derived growth factor receptor studied using a monoclonal antibody. J Biol Chem. 1987 Aug 5;262(22):10780–10785. [PubMed] [Google Scholar]
  28. Heldin C. H., Bäckström G., Ostman A., Hammacher A., Rönnstrand L., Rubin K., Nistér M., Westermark B. Binding of different dimeric forms of PDGF to human fibroblasts: evidence for two separate receptor types. EMBO J. 1988 May;7(5):1387–1393. doi: 10.1002/j.1460-2075.1988.tb02955.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  29. Hemler M. E. VLA proteins in the integrin family: structures, functions, and their role on leukocytes. Annu Rev Immunol. 1990;8:365–400. doi: 10.1146/annurev.iy.08.040190.002053. [DOI] [PubMed] [Google Scholar]
  30. Herman B., Harrington M. A., Olashaw N. E., Pledger W. J. Identification of the cellular mechanisms responsible for platelet-derived growth factor induced alterations in cytoplasmic vinculin distribution. J Cell Physiol. 1986 Jan;126(1):115–125. doi: 10.1002/jcp.1041260116. [DOI] [PubMed] [Google Scholar]
  31. Huang S. S., Huang J. S. Rapid turnover of the platelet-derived growth factor receptor in sis-transformed cells and reversal by suramin. Implications for the mechanism of autocrine transformation. J Biol Chem. 1988 Sep 5;263(25):12608–12618. [PubMed] [Google Scholar]
  32. Hynes R. O. Integrins: versatility, modulation, and signaling in cell adhesion. Cell. 1992 Apr 3;69(1):11–25. doi: 10.1016/0092-8674(92)90115-s. [DOI] [PubMed] [Google Scholar]
  33. Ingber D. Integrins as mechanochemical transducers. Curr Opin Cell Biol. 1991 Oct;3(5):841–848. doi: 10.1016/0955-0674(91)90058-7. [DOI] [PubMed] [Google Scholar]
  34. Johnsson A., Betsholtz C., Heldin C. H., Westermark B. Antibodies against platelet-derived growth factor inhibit acute transformation by simian sarcoma virus. Nature. 1985 Oct 3;317(6036):438–440. doi: 10.1038/317438a0. [DOI] [PubMed] [Google Scholar]
  35. Juliano R. L., Haskill S. Signal transduction from the extracellular matrix. J Cell Biol. 1993 Feb;120(3):577–585. doi: 10.1083/jcb.120.3.577. [DOI] [PMC free article] [PubMed] [Google Scholar]
  36. Kanakura Y., Druker B., DiCarlo J., Cannistra S. A., Griffin J. D. Phorbol 12-myristate 13-acetate inhibits granulocyte-macrophage colony stimulating factor-induced protein tyrosine phosphorylation in a human factor-dependent hematopoietic cell line. J Biol Chem. 1991 Jan 5;266(1):490–495. [PubMed] [Google Scholar]
  37. Klein C. E., Dressel D., Steinmayer T., Mauch C., Eckes B., Krieg T., Bankert R. B., Weber L. Integrin alpha 2 beta 1 is upregulated in fibroblasts and highly aggressive melanoma cells in three-dimensional collagen lattices and mediates the reorganization of collagen I fibrils. J Cell Biol. 1991 Dec;115(5):1427–1436. doi: 10.1083/jcb.115.5.1427. [DOI] [PMC free article] [PubMed] [Google Scholar]
  38. Kornberg L., Juliano R. L. Signal transduction from the extracellular matrix: the integrin-tyrosine kinase connection. Trends Pharmacol Sci. 1992 Mar;13(3):93–95. doi: 10.1016/0165-6147(92)90034-4. [DOI] [PubMed] [Google Scholar]
  39. La Rocca R. V., Stein C. A., Myers C. E. Suramin: prototype of a new generation of antitumor compounds. Cancer Cells. 1990 Apr;2(4):106–115. [PubMed] [Google Scholar]
  40. Laemmli U. K. Cleavage of structural proteins during the assembly of the head of bacteriophage T4. Nature. 1970 Aug 15;227(5259):680–685. doi: 10.1038/227680a0. [DOI] [PubMed] [Google Scholar]
  41. Lansman J. B. Endothelial mechanosensors. Going with the flow. Nature. 1988 Feb 11;331(6156):481–482. doi: 10.1038/331481a0. [DOI] [PubMed] [Google Scholar]
  42. Lee R. T., Berditchevski F., Cheng G. C., Hemler M. E. Integrin-mediated collagen matrix reorganization by cultured human vascular smooth muscle cells. Circ Res. 1995 Feb;76(2):209–214. doi: 10.1161/01.res.76.2.209. [DOI] [PubMed] [Google Scholar]
  43. Lin Y. C., Grinnell F. Decreased level of PDGF-stimulated receptor autophosphorylation by fibroblasts in mechanically relaxed collagen matrices. J Cell Biol. 1993 Aug;122(3):663–672. doi: 10.1083/jcb.122.3.663. [DOI] [PMC free article] [PubMed] [Google Scholar]
  44. McNamee H. P., Ingber D. E., Schwartz M. A. Adhesion to fibronectin stimulates inositol lipid synthesis and enhances PDGF-induced inositol lipid breakdown. J Cell Biol. 1993 May;121(3):673–678. doi: 10.1083/jcb.121.3.673. [DOI] [PMC free article] [PubMed] [Google Scholar]
  45. Mellström K., Heldin C. H., Westermark B. Induction of circular membrane ruffling on human fibroblasts by platelet-derived growth factor. Exp Cell Res. 1988 Aug;177(2):347–359. doi: 10.1016/0014-4827(88)90468-5. [DOI] [PubMed] [Google Scholar]
  46. Miekka S. I., Ingham K. C., Menache D. Rapid methods for isolation of human plasma fibronectin. Thromb Res. 1982 Jul 1;27(1):1–14. doi: 10.1016/0049-3848(82)90272-9. [DOI] [PubMed] [Google Scholar]
  47. Mochitate K., Pawelek P., Grinnell F. Stress relaxation of contracted collagen gels: disruption of actin filament bundles, release of cell surface fibronectin, and down-regulation of DNA and protein synthesis. Exp Cell Res. 1991 Mar;193(1):198–207. doi: 10.1016/0014-4827(91)90556-a. [DOI] [PubMed] [Google Scholar]
  48. Ostman A., Bäckström G., Fong N., Betsholtz C., Wernstedt C., Hellman U., Westermark B., Valenzuela P., Heldin C. H. Expression of three recombinant homodimeric isoforms of PDGF in Saccharomyces cerevisiae: evidence for difference in receptor binding and functional activities. Growth Factors. 1989;1(3):271–281. doi: 10.3109/08977198908998003. [DOI] [PubMed] [Google Scholar]
  49. Rankin S., Rozengurt E. Platelet-derived growth factor modulation of focal adhesion kinase (p125FAK) and paxillin tyrosine phosphorylation in Swiss 3T3 cells. Bell-shaped dose response and cross-talk with bombesin. J Biol Chem. 1994 Jan 7;269(1):704–710. [PubMed] [Google Scholar]
  50. Reuterdahl C., Tingström A., Terracio L., Funa K., Heldin C. H., Rubin K. Characterization of platelet-derived growth factor beta-receptor expressing cells in the vasculature of human rheumatoid synovium. Lab Invest. 1991 Mar;64(3):321–329. [PubMed] [Google Scholar]
  51. Rubin K., Gullberg D., Borg T. K., Obrink B. Hepatocyte adhesion to collagen. Isolation of membrane glycoproteins involved in adhesion to collagen. Exp Cell Res. 1986 May;164(1):127–138. doi: 10.1016/0014-4827(86)90460-x. [DOI] [PubMed] [Google Scholar]
  52. Ruoslahti E. Integrins. J Clin Invest. 1991 Jan;87(1):1–5. doi: 10.1172/JCI114957. [DOI] [PMC free article] [PubMed] [Google Scholar]
  53. Rönnstrand L., Terracio L., Claesson-Welsh L., Heldin C. H., Rubin K. Characterization of two monoclonal antibodies reactive with the external domain of the platelet-derived growth factor receptor. J Biol Chem. 1988 Jul 25;263(21):10429–10435. [PubMed] [Google Scholar]
  54. Schaller M. D., Borgman C. A., Cobb B. S., Vines R. R., Reynolds A. B., Parsons J. T. pp125FAK a structurally distinctive protein-tyrosine kinase associated with focal adhesions. Proc Natl Acad Sci U S A. 1992 Jun 1;89(11):5192–5196. doi: 10.1073/pnas.89.11.5192. [DOI] [PMC free article] [PubMed] [Google Scholar]
  55. Schiro J. A., Chan B. M., Roswit W. T., Kassner P. D., Pentland A. P., Hemler M. E., Eisen A. Z., Kupper T. S. Integrin alpha 2 beta 1 (VLA-2) mediates reorganization and contraction of collagen matrices by human cells. Cell. 1991 Oct 18;67(2):403–410. doi: 10.1016/0092-8674(91)90191-z. [DOI] [PubMed] [Google Scholar]
  56. Schwartz M. A., Ingber D. E. Integrating with integrins. Mol Biol Cell. 1994 Apr;5(4):389–393. doi: 10.1091/mbc.5.4.389. [DOI] [PMC free article] [PubMed] [Google Scholar]
  57. Schwartz M. A., Lechene C. Adhesion is required for protein kinase C-dependent activation of the Na+/H+ antiporter by platelet-derived growth factor. Proc Natl Acad Sci U S A. 1992 Jul 1;89(13):6138–6141. doi: 10.1073/pnas.89.13.6138. [DOI] [PMC free article] [PubMed] [Google Scholar]
  58. Schwartz M. A. Transmembrane signalling by integrins. Trends Cell Biol. 1992 Oct;2(10):304–308. doi: 10.1016/0962-8924(92)90120-c. [DOI] [PubMed] [Google Scholar]
  59. Seifert R. A., Hart C. E., Phillips P. E., Forstrom J. W., Ross R., Murray M. J., Bowen-Pope D. F. Two different subunits associate to create isoform-specific platelet-derived growth factor receptors. J Biol Chem. 1989 May 25;264(15):8771–8778. [PubMed] [Google Scholar]
  60. Serve H., Yee N. S., Stella G., Sepp-Lorenzino L., Tan J. C., Besmer P. Differential roles of PI3-kinase and Kit tyrosine 821 in Kit receptor-mediated proliferation, survival and cell adhesion in mast cells. EMBO J. 1995 Feb 1;14(3):473–483. doi: 10.1002/j.1460-2075.1995.tb07023.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  61. Shiraishi T., Morimoto S., Itoh K., Sato H., Sugihara K., Onishi T., Ogihara T. Radioimmunoassay of human platelet-derived growth factor using monoclonal antibody toward a synthetic 73-97 fragment of its B-chain. Clin Chim Acta. 1989 Sep 15;184(1):65–74. doi: 10.1016/0009-8981(89)90257-x. [DOI] [PubMed] [Google Scholar]
  62. Skinner M. P., Raines E. W., Ross R. Dynamic expression of alpha 1 beta 1 and alpha 2 beta 1 integrin receptors by human vascular smooth muscle cells. Alpha 2 beta 1 integrin is required for chemotaxis across type I collagen-coated membranes. Am J Pathol. 1994 Nov;145(5):1070–1081. [PMC free article] [PubMed] [Google Scholar]
  63. Sorkin A., Westermark B., Heldin C. H., Claesson-Welsh L. Effect of receptor kinase inactivation on the rate of internalization and degradation of PDGF and the PDGF beta-receptor. J Cell Biol. 1991 Feb;112(3):469–478. doi: 10.1083/jcb.112.3.469. [DOI] [PMC free article] [PubMed] [Google Scholar]
  64. Takada Y., Wayner E. A., Carter W. G., Hemler M. E. Extracellular matrix receptors, ECMRII and ECMRI, for collagen and fibronectin correspond to VLA-2 and VLA-3 in the VLA family of heterodimers. J Cell Biochem. 1988 Aug;37(4):385–393. doi: 10.1002/jcb.240370406. [DOI] [PubMed] [Google Scholar]
  65. Tingström A., Heldin C. H., Rubin K. Regulation of fibroblast-mediated collagen gel contraction by platelet-derived growth factor, interleukin-1 alpha and transforming growth factor-beta 1. J Cell Sci. 1992 Jun;102(Pt 2):315–322. doi: 10.1242/jcs.102.2.315. [DOI] [PubMed] [Google Scholar]
  66. Tingström A., Reuterdahl C., Lindahl P., Heldin C. H., Rubin K. Expression of platelet-derived growth factor-beta receptors on human fibroblasts. Regulation by recombinant platelet-derived growth factor-BB, IL-1, and tumor necrosis factor-alpha. J Immunol. 1992 Jan 15;148(2):546–554. [PubMed] [Google Scholar]
  67. Tomasek J. J., Hay E. D. Analysis of the role of microfilaments and microtubules in acquisition of bipolarity and elongation of fibroblasts in hydrated collagen gels. J Cell Biol. 1984 Aug;99(2):536–549. doi: 10.1083/jcb.99.2.536. [DOI] [PMC free article] [PubMed] [Google Scholar]
  68. Turner C. E. Paxillin: a cytoskeletal target for tyrosine kinases. Bioessays. 1994 Jan;16(1):47–52. doi: 10.1002/bies.950160107. [DOI] [PubMed] [Google Scholar]
  69. Wang N., Butler J. P., Ingber D. E. Mechanotransduction across the cell surface and through the cytoskeleton. Science. 1993 May 21;260(5111):1124–1127. doi: 10.1126/science.7684161. [DOI] [PubMed] [Google Scholar]
  70. Wayner E. A., Carter W. G., Piotrowicz R. S., Kunicki T. J. The function of multiple extracellular matrix receptors in mediating cell adhesion to extracellular matrix: preparation of monoclonal antibodies to the fibronectin receptor that specifically inhibit cell adhesion to fibronectin and react with platelet glycoproteins Ic-IIa. J Cell Biol. 1988 Nov;107(5):1881–1891. doi: 10.1083/jcb.107.5.1881. [DOI] [PMC free article] [PubMed] [Google Scholar]
  71. Williams L. T. Signal transduction by the platelet-derived growth factor receptor. Science. 1989 Mar 24;243(4898):1564–1570. doi: 10.1126/science.2538922. [DOI] [PubMed] [Google Scholar]
  72. Zhu X., Assoian R. K. Integrin-dependent activation of MAP kinase: a link to shape-dependent cell proliferation. Mol Biol Cell. 1995 Mar;6(3):273–282. doi: 10.1091/mbc.6.3.273. [DOI] [PMC free article] [PubMed] [Google Scholar]
  73. von der Mark K., von der Mark H., Goodman S. Cellular responses to extracellular matrix. Kidney Int. 1992 Mar;41(3):632–640. doi: 10.1038/ki.1992.97. [DOI] [PubMed] [Google Scholar]

Articles from The Journal of Cell Biology are provided here courtesy of The Rockefeller University Press

RESOURCES