Identification of SH2B1β as a focal adhesion protein that regulates focal adhesion size and number
Identification of SH2B1β as a focal adhesion protein that regulates focal adhesion size and number
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DOI：
10.1242/jcs.081547
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发表时间：
2011-09-15
影响因子：
4
通讯作者：
Carter-Su, Christin
中科院分区：
文献类型：
--
作者：
Lanning, Nathan J.;Su, Hsiao-Wen;Carter-Su, Christin
适配蛋白SH2B1β参与了细胞迁移和分化等过程中肌动蛋白细胞骨架的调节。在这里，我们确定SH2B1β是一种新的粘着斑蛋白。我们提供了佛波醇12-肉豆蔻酸酯(PMA)诱导的蛋白激酶C(PKC)激活反应中SH2B1β被磷酸化的证据，并表明PMA诱导SH2B1β迅速重新分布出局灶性粘连。我们还表明，生长激素(GH)增加SH2B1β进入和离开局灶性粘连的循环。SH2B1β中的Ser161和Ser165属于公认的PKC底物基序。将这两个丝氨酸残基突变为丙氨酸残基可以消除PMA诱导的SH2B1β在局部粘连中的重新分布，减少对照和GH刺激细胞中SH2B1β循环进入和离开局部粘连，并增加局部粘连的大小。相比之下，将Ser165突变为谷氨酸残基会减少局灶性粘连中SH2B1β的数量，并增加每个细胞的局灶性粘连数量。这些结果表明，PKC的激活通过Ser161和/或Ser165的磷酸化来调节SH2B1β焦点黏附的定位。SH2B1β的磷酸化增加了灶性粘连的数量，这一发现提示了SH2B1β刺激细胞运动的机制。
The adaptor protein SH2B1 beta participates in regulation of the actin cytoskeleton during processes such as cell migration and differentiation. Here, we identify SH2B1 beta as a new focal adhesion protein. We provide evidence that SH2B1 beta is phosphorylated in response to phorbol 12-myristate 13-acetate (PMA)-induced protein kinase C (PKC) activation and show that PMA induces a rapid redistribution of SH2B1 beta out of focal adhesions. We also show that growth hormone (GH) increases cycling of SH2B1 beta into and out of focal adhesions. Ser161 and Ser165 in SH2B1 beta fall within consensus PKC substrate motifs. Mutating these two serine residues into alanine residues abrogates PMA-induced redistribution of SH2B1 beta out of focal adhesions, decreases SH2B1 beta cycling into and out of focal adhesions in control and GH-stimulated cells, and increases the size of focal adhesions. By contrast, mutating Ser165 into a glutamate residue decreases the amount of SH2B1 beta in focal adhesions and increases the number of focal adhesions per cell. These results suggest that activation of PKC regulates SH2B1 beta focal adhesion localization through phosphorylation of Ser161 and/or Ser165. The finding that phosphorylation of SH2B1 beta increases the number of focal adhesions suggests a mechanism for the stimulatory effect on cell motility of SH2B1 beta.