Inducible tyrosine phosphorylation of the beta3 integrin requires the alphaV integrin cytoplasmic tail.
We have found that the integrin beta3 chain can be phosphorylated on tyrosine residues in K562 cells transfected with alphavbeta3. Tyrosine phosphorylation of the beta3 cytoplasmic tail is induced by adhesion to alphavbeta3-specific ligand or antibody or by incubation in manganese-containing buffer. Under the same conditions, beta5 does not become tyrosine-phosphorylated in K562 transfected with alphavbeta5. Phosphorylation of the beta3 subunit requires the simultaneous presence of the alphav subunit cytoplasmic tail, because neither the alphaIIb subunit nor a truncated alphav subunit is sufficient to permit phosphorylation of beta3 when coexpressed as a heterodimer with beta3. Finally, tyrosine phosphorylation of the beta3 cytoplasmic tail occurs on both human and murine beta3 and is inducible in the ovarian carcinoma OV10 as well, independent of expression of integrin-associated protein (CD47). Tyrosine phosphorylation of the beta3 integrin subunit facilitates association of Grb-2, an adaptor protein leading to activation of the Ras signaling pathway, and may contribute to the unique functional and signaling capabilities of alphavbeta3.
Blystone
S D
SD
Department of Medicine, Infectious Diseases Division, Missouri, 63110, USA. ebrown@id.wustl.edu
Lindberg
F P
FP
Williams
M P
MP
McHugh
K P
KP
Brown
E J
EJ
D048868:Adaptor Proteins, Signal Transducing; D000818:Animals; D015703:Antigens, CD / Q000378:metabolism*; D005260:Female; D051380:GRB2 Adaptor Protein; D006801:Humans; D039564:Integrin alphaV; D039661:Integrin beta3; D016023:Integrins / Q000378:metabolism*; D051379:Mice; D010051:Ovarian Neoplasms / Q000378:metabolism; D010766:Phosphorylation; D019000:Phosphotyrosine / Q000276:immunology; D010980:Platelet Membrane Glycoproteins / Q000378:metabolism*; D011505:Protein-Tyrosine Kinases / Q000378:metabolism*; D011506:Proteins / Q000378:metabolism; D013329:Structure-Activity Relationship; D014407:Tumor Cells, Cultured; D018631:ras Proteins / Q000378:metabolism
D048868:Adaptor Proteins, Signal Transducing; D015703:Antigens, CD; D051380:GRB2 Adaptor Protein; C495948:GRB2 protein, human; C495949:Grb2 protein, mouse; D039564:Integrin alphaV; D039661:Integrin beta3; D016023:Integrins; D010980:Platelet Membrane Glycoproteins; D011506:Proteins; D019000:Phosphotyrosine; D011505:Protein-Tyrosine Kinases; D018631:ras Proteins