Stimulation of tyrosine phosphorylation and accumulation of GTP-bound p21ras upon antibody-mediated alpha 2 beta 1 integrin activation in T-lymphoblastic cells.
Integrins are a family of heterodimeric integral plasma membrane proteins that behave as receptors for components of the extracellular matrix and also mediate cell to cell adhesion. Occupation of integrins can result in the transduction of intracellular signals, leading to cytoskeletal reorganization, tyrosine phosphorylation, and induction of gene expression. We report here that the ligation of alpha 2 beta 1 integrin by collagen-adhesion stimulatory anti-alpha 2 and anti-beta 1 antibodies resulted in the accumulation of p21ras in the active GTP-bound state in Jurkat T-lymphoblastoid cells. The activation was accompanied by the tyrosine phosphorylation of proteins of 47-52 kDa. This stimulation of tyrosine phosphorylation and p21ras activation was specific for the activating antibodies and occurred within 2 min of the addition of these antibodies. Although treatment of the cells with the protein kinase C activator, phorbol 12-myristate 13-acetate also resulted in an induction of both cell attachment to collagen and of p21ras activation, tyrosine phosphorylation was not observed. These results demonstrate that alpha 2 beta 1 integrin activation can result in the specific stimulation of tyrosine phosphorylation of 47-52-kDa proteins, as well as activation of a signaling pathway involving p21ras.
Kapron-Bras
C
C
Department of Cancer Research, Sunnybrook Health Science Centre, Toronto, Ontario, Canada.
Fitz-Gibbon
L
L
Jeevaratnam
P
P
Wilkins
J
J
Dedhar
S
S
D000906:Antibodies / Q000276:immunology; D002448:Cell Adhesion; D002478:Cells, Cultured; D003094:Collagen / Q000378:metabolism; D019204:GTP-Binding Proteins / Q000378:metabolism*; D006801:Humans; D016023:Integrins / Q000276:immunology / Q000378:metabolism*; D010766:Phosphorylation; D016283:Proto-Oncogene Proteins p21(ras) / Q000378:metabolism*; D013601:T-Lymphocytes / Q000378:metabolism*; D014443:Tyrosine / Q000378:metabolism*
D000906:Antibodies; D016023:Integrins; D014443:Tyrosine; D003094:Collagen; D019204:GTP-Binding Proteins; C501009:HRAS protein, human; D016283:Proto-Oncogene Proteins p21(ras)