Alphavbeta3 integrin associates with activated insulin and PDGFbeta receptors and potentiates the biological activity of PDGF.
Integrin-mediated cell attachment modulates growth responses and growth factors regulate cell attachment. Moreover, both cell attachment to extracellular matrix and mitogenic signaling by growth factors are necessary for the proliferation of most types of normal cells, suggesting that integrin and growth factor receptor signaling pathways meet at some downstream point. We report here that a small, highly tyrosine-phosphorylated fraction of PDGFbeta and insulin receptors co-immunoprecipitates with the alphavbeta3 integrin from cells. The integrin association requires growth factor stimulation of the receptors. Several signaling molecules that are known to be associated with activated growth factor receptors were present in the alphavbeta3 integrin complexes. Mitogenicity and chemotaxis induced by PDGF-BB were enhanced in cells plated on the alphavbeta3 ligand vitronectin compared with cells plated on the beta1 integrin ligand collagen. Thus, the engagement of the alphavbeta3 integrin in cell-matrix interactions appears to coordinate an intense response to growth factors, helping to explain the importance of this integrin for tissue regeneration, angiogenesis and tumor metastasis.
Schneller
M
M
La Jolla Cancer Research Center, The Burnham Institute, 10901 North Torrey Pines Road, La Jolla, CA 92037, USA.
Vuori
K
K
Ruoslahti
E
E
D016475:3T3 Cells; D000818:Animals; D000906:Antibodies / Q000494:pharmacology; D000911:Antibodies, Monoclonal / Q000494:pharmacology; D000077214:Becaplermin; D002448:Cell Adhesion / Q000187:drug effects / Q000502:physiology; D002455:Cell Division / Q000187:drug effects; D002460:Cell Line; D002478:Cells, Cultured; D002633:Chemotaxis / Q000187:drug effects / Q000502:physiology; D005109:Extracellular Matrix / Q000502:physiology; D006801:Humans; D008297:Male; D051379:Mice; D010982:Platelet-Derived Growth Factor / Q000494:pharmacology*; D020574:Proto-Oncogene Proteins c-sis; D051381:Rats; D011972:Receptor, Insulin / Q000502:physiology*; D020797:Receptor, Platelet-Derived Growth Factor beta; D017479:Receptors, Platelet-Derived Growth Factor / Q000276:immunology / Q000502:physiology*; D019030:Receptors, Vitronectin / Q000276:immunology / Q000502:physiology*; D015398:Signal Transduction; D012867:Skin
D000906:Antibodies; D000911:Antibodies, Monoclonal; D010982:Platelet-Derived Growth Factor; D020574:Proto-Oncogene Proteins c-sis; D019030:Receptors, Vitronectin; D000077214:Becaplermin; D011972:Receptor, Insulin; D020797:Receptor, Platelet-Derived Growth Factor beta; D017479:Receptors, Platelet-Derived Growth Factor