Anchorage-dependent regulation of the mitogen-activated protein kinase cascade by growth factors is supported by a variety of integrin alpha chains.
Integrin cooperation with growth factor receptors to enable permissive signaling to the mitogen-activated protein (MAP) kinase pathway has important implications for cell proliferation, differentiation, and survival. Here we have sought to determine whether anchorage regulation of the MAP kinase pathway is specific to the alpha chain subunit of the integrins employed during adhesion. Human umbilical vein endothelial cells (HUVECs) anchored via endogenous alpha(2), alpha(3), or alpha(5) integrin subunits or NIH3T3 fibroblast cells lines anchored via ectopically expressed human integrin alpha(2) or alpha(5) subunits displayed comparable MAP kinase activation upon growth factor stimulation, regardless of the integrin alpha chain employed. In contrast, when either cell type was maintained in suspension, growth factor treatment inefficiently activated the MAP kinase pathway. The integrin-mediated enhancement of MAP kinase activation by growth factor correlated with the tyrosine phosphorylation of focal adhesion kinase but was independent of Shc. These data indicate that integrin modulation of the MAP kinase pathway is supported by a variety of integrin complexes and imply that other pathways may be required for the previously reported alpha chain-specific effects on cell cycle regulation and cell differentiation.
Aplin
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Department of Pharmacology, School of Medicine, University of North Carolina, Chapel Hill, North Carolina 27599, USA.
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Juliano
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RL
D016475:3T3 Cells; D048868:Adaptor Proteins, Signal Transducing; D033942:Adaptor Proteins, Vesicular Transport; D000818:Animals; D015703:Antigens, CD / Q000235:genetics / Q000378:metabolism; D002448:Cell Adhesion / Q000502:physiology*; D015815:Cell Adhesion Molecules / Q000378:metabolism; D004730:Endothelium, Vascular / Q000166:cytology; D004815:Epidermal Growth Factor / Q000494:pharmacology; D051417:Focal Adhesion Kinase 1; D051416:Focal Adhesion Protein-Tyrosine Kinases; D006133:Growth Substances / Q000494:pharmacology*; D006801:Humans; D039421:Integrin alpha2; D039422:Integrin alpha3; D039482:Integrin alpha5; D016023:Integrins / Q000378:metabolism*; D020935:MAP Kinase Signaling System; D051379:Mice; D011505:Protein-Tyrosine Kinases / Q000378:metabolism; D011506:Proteins / Q000378:metabolism; D011994:Recombinant Proteins / Q000378:metabolism; D055765:Shc Signaling Adaptor Proteins; D000071425:Src Homology 2 Domain-Containing, Transforming Protein 1
D048868:Adaptor Proteins, Signal Transducing; D033942:Adaptor Proteins, Vesicular Transport; D015703:Antigens, CD; D015815:Cell Adhesion Molecules; D006133:Growth Substances; D039421:Integrin alpha2; D039422:Integrin alpha3; D039482:Integrin alpha5; D016023:Integrins; D011506:Proteins; D011994:Recombinant Proteins; C528024:SHC1 protein, human; D055765:Shc Signaling Adaptor Proteins; C528034:Shc1 protein, mouse; D000071425:Src Homology 2 Domain-Containing, Transforming Protein 1; D004815:Epidermal Growth Factor; D011505:Protein-Tyrosine Kinases; D051417:Focal Adhesion Kinase 1; D051416:Focal Adhesion Protein-Tyrosine Kinases; C496050:PTK2 protein, human; C496051:Ptk2 protein, mouse