Integrin α2β1 promotes activation of protein phosphatase 2A and dephosphorylation of Akt and glycogen synthase kinase 3β
Integrin α2β1 promotes activation of protein phosphatase 2A and dephosphorylation of Akt and glycogen synthase kinase 3β
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DOI：
10.1128/mcb.22.5.1352-1359.2002
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发表时间：
2002-03-01
影响因子：
5.3
通讯作者：
Heino, J
中科院分区：
文献类型：
--
作者：
Ivaska, J;Nissinen, L;Heino, J
丝氨酸/苏氨酸激酶Akt是磷脂酰肌醇-3-激酶（PI-3 K）的下游效应蛋白。许多整联蛋白可以作为PI-3 K/Akt途径的正调节剂起作用。整合素α 2 β 1是一种胶原蛋白受体，已显示其诱导不同于由其他整合素激活的特异性信号。在这里，我们发现，在对比发现的细胞粘附到纤连蛋白，α 2 β 1介导的细胞粘附到胶原蛋白导致Akt和糖原合成酶激酶3 β（GSK 3 β）的去磷酸化，并伴随着蛋白丝氨酸/苏氨酸磷酸酶2A（PP 2A）活性的诱导。PP 2A活化可通过α 2胞质结构域中的突变和功能阻断性抗α 2抗体来抑制。Akt可以与PP 2A共沉淀，并且Akt与PP 2Ac（催化亚基）的共表达抑制Akt激酶活性。PP 2A的整合素α 2 β 1相关激活依赖于Cdc 42。这些结果表明，细胞粘附到胶原蛋白调节Akt的活性，通过α 2 β 1诱导的激活PP 2A。
Serine/threonine kinase Akt is a downstream effector protein of phosphatidylinositol-3-kinase (PI-3K). Many integrins can function as positive modulators of the PI-3K/Akt pathway. Integrin alpha2beta1 is a collagen receptor that has been shown to induce specific signals distinct from those activated by other integrins. Here, we found that, in contrast what was found for cells adherent to fibronectin, alpha2beta1-mediated cell adhesion to collagen leads to dephosphorylation of Akt and glycogen synthase kinase 3beta (GSK3beta) and concomitantly to the induction of protein serine/threonine phosphatase 2A (PP2A) activity. PP2A activation can be inhibited by mutation in the alpha2 cytoplasmic domain and by a function-blocking anti-alpha2 antibody. Akt can be coprecipitated with PP2A, and coexpression of Akt with PP2Ac (catalytic subunit) inhibits Akt kinase activity. Integrin alpha2beta1-related activation of PP2A is dependent on Cdc42. These results indicate that cell adhesion to collagen modulates Akt activity via the alpha2beta1-induced activation of PP2A.