Kapron-Bras C, Fitz-Gibbon L, Jeevaratnam P, Wilkins J, Dedhar S
Department of Cancer Research, Sunnybrook Health Science Centre, Toronto, Ontario, Canada.
J Biol Chem. 1993 Oct 5;268(28):20701-4.
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.
整合素是一类异二聚体整合质膜蛋白家族，它们作为细胞外基质成分的受体，还介导细胞间黏附。整合素的激活可导致细胞内信号转导，引起细胞骨架重组、酪氨酸磷酸化以及基因表达的诱导。我们在此报告，通过胶原黏附刺激抗α2和抗β1抗体连接α2β1整合素，导致Jurkat T淋巴母细胞中p21ras以活性GTP结合状态积累。这种激活伴随着47 - 52 kDa蛋白质的酪氨酸磷酸化。酪氨酸磷酸化和p21ras激活的这种刺激对激活抗体具有特异性，并且在添加这些抗体后2分钟内发生。虽然用蛋白激酶C激活剂佛波醇12 - 肉豆蔻酸酯13 - 乙酸酯处理细胞也导致细胞对胶原的附着和p21ras激活的诱导，但未观察到酪氨酸磷酸化。这些结果表明α2β1整合素激活可导致对47 - 52 kDa蛋白质酪氨酸磷酸化的特异性刺激，以及涉及p21ras的信号通路的激活。
