A requirement for caveolin-1 and associated kinase Fyn in integrin signaling and anchorage-dependent cell growth.
Caveolin-1 functions as a membrane adaptor to link the integrin alpha subunit to the tyrosine kinase Fyn. Upon integrin ligation, Fyn is activated and binds, via its SH3 domain, to Shc. Shc is subsequently phosphorylated at tyrosine 317 and recruits Grb2. This sequence of events is necessary to couple integrins to the Ras-ERK pathway and promote cell cycle progression. These findings reveal an unexpected function of caveolin-1 and Fyn in integrin signaling and anchorage-dependent cell growth.
Wary
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Cellular Biochemistry and Biophysics Program, Memorial Sloan-Kettering Cancer Center, New York, New York 10021, USA.
Mariotti
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Zurzolo
C
C
Giancotti
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FG
D016475:3T3 Cells; D048868:Adaptor Proteins, Signal Transducing; D033942:Adaptor Proteins, Vesicular Transport; D000818:Animals; D051242:Caveolin 1; D022461:Caveolins; D002455:Cell Division / Q000502:physiology; D002458:Cell Fractionation; D002478:Cells, Cultured; D051380:GRB2 Adaptor Protein; D016023:Integrins / Q000302:isolation & purification / Q000502:physiology*; D008565:Membrane Proteins / Q000302:isolation & purification / Q000502:physiology*; D051379:Mice; D020928:Mitogen-Activated Protein Kinases / Q000502:physiology; D017830:Octoxynol; D011505:Protein-Tyrosine Kinases / Q000302:isolation & purification / Q000502:physiology*; D011506:Proteins / Q000502:physiology; D011518:Proto-Oncogene Proteins / Q000737:chemistry / Q000302:isolation & purification / Q000502:physiology*; D051076:Proto-Oncogene Proteins c-fyn; D051381:Rats; D011916:Rats, Inbred F344; D055765:Shc Signaling Adaptor Proteins; D015398:Signal Transduction / Q000502:physiology*; D012995:Solubility; D000071425:Src Homology 2 Domain-Containing, Transforming Protein 1; D013961:Thyroid Gland / Q000166:cytology; D018631:ras Proteins / Q000502:physiology; D018909:src Homology Domains / Q000502:physiology
D048868:Adaptor Proteins, Signal Transducing; D033942:Adaptor Proteins, Vesicular Transport; C495541:Cav1 protein, mouse; C495537:Cav1 protein, rat; D051242:Caveolin 1; D022461:Caveolins; D051380:GRB2 Adaptor Protein; C495949:Grb2 protein, mouse; C495950:Grb2 protein, rat; D016023:Integrins; D008565:Membrane Proteins; D011506:Proteins; D011518:Proto-Oncogene Proteins; D055765:Shc Signaling Adaptor Proteins; C528034:Shc1 protein, mouse; C528035:Shc1 protein, rat; D000071425:Src Homology 2 Domain-Containing, Transforming Protein 1; D017830:Octoxynol; D011505:Protein-Tyrosine Kinases; C494960:Fyn protein, mouse; C494961:Fyn protein, rat; D051076:Proto-Oncogene Proteins c-fyn; D020928:Mitogen-Activated Protein Kinases; D018631:ras Proteins