Identification of SH2B1? as a focal adhesion protein that regulates focal adhesion size and number.

ABSTRACT: The adaptor protein SH2B1? participates in regulation of the actin cytoskeleton during processes such as cell migration and differentiation. Here, we identify SH2B1? as a new focal adhesion protein. We provide evidence that SH2B1? 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? out of focal adhesions. We also show that growth hormone (GH) increases cycling of SH2B1? into and out of focal adhesions. Ser161 and Ser165 in SH2B1? fall within consensus PKC substrate motifs. Mutating these two serine residues into alanine residues abrogates PMA-induced redistribution of SH2B1? out of focal adhesions, decreases SH2B1? 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? in focal adhesions and increases the number of focal adhesions per cell. These results suggest that activation of PKC regulates SH2B1? focal adhesion localization through phosphorylation of Ser161 and/or Ser165. The finding that phosphorylation of SH2B1? increases the number of focal adhesions suggests a mechanism for the stimulatory effect on cell motility of SH2B1?.

SUBMITTER: Lanning NJ 

PROVIDER: S-EPMC3172186 | biostudies-literature | 2011 Sep

REPOSITORIES: biostudies-literature