Targeting membrane-localized focal adhesion kinase to focal adhesions - Roles of tyrosine phosphorylation and Src family kinases
Targeting membrane-localized focal adhesion kinase to focal adhesions - Roles of tyrosine phosphorylation and Src family kinases
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DOI：
10.1074/jbc.m212396200
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发表时间：
2003-08-01
影响因子：
4.8
通讯作者：
Yamada, KM
中科院分区：
文献类型：
--
作者：
Katz, BZ;Romer, L;Yamada, KM
在本研究中，我们检查了粘着斑中活化的粘着斑激酶定位的调节。通过使用与惰性跨膜锚融合的粘着斑激酶，我们发现粘着斑激酶内的焦点接触靶向区域被保留在膜靶向融合蛋白中。然而，在酪氨酸磷酸化后，全长粘着斑激酶被排除在粘着斑之外。这种定位的负调节可以通过使先前显示参与粘附介导的信号转导的粘着斑激酶的关键氨基酸残基发生突变来消除。过钒酸盐诱导的内源性粘着斑激酶的过度磷酸化导致粘着斑定位的类似减少。我们还在此表明，Src 家族激酶对于磷酸化依赖性粘着斑激酶从粘着斑中的排除至关重要。我们在此提出了一种分子模型，用于涉及 Src 激酶和 C 端 (Tyr-925) 酪氨酸残基的抑制性磷酸化的粘着斑激酶组织的酪氨酸磷酸化依赖性调节。
In the present study, we examined regulation of activated focal adhesion kinase localization in focal adhesions. By using focal adhesion kinase fused to an inert transmembrane anchor, we found that the focal contact targeting region within focal adhesion kinase was preserved in the membrane-targeted fusion protein. However, upon tyrosine phosphorylation, full-length focal adhesion kinase became excluded from focal adhesions. This negative regulation of localization could be abolished by mutating key amino acid residues of focal adhesion kinase shown previously to be involved in adhesion-mediated signal transduction. Hyper-phosphorylation of endogenous focal adhesion kinase induced by pervanadate resulted in a similar reduction of localization at focal adhesions. We also show here that Src family kinases are essential for the phosphorylation-dependent exclusion of focal adhesion kinase from focal adhesions. We propose here a molecular model for the tyrosine phosphorylation-dependent regulation of focal adhesion kinase organization involving Src kinases and an inhibitory phosphorylation of the C-terminal (Tyr-925) tyrosine residue.