title: Identification of SH2B1β as a focal adhesion protein that regulates focal adhesion size and number.
abstract: The adaptor protein SH2B1β participates in regulation of the actin cytoskeleton during processes such as cell migration and differentiation. Here, we identify SH2B1β as a new focal adhesion protein. We provide evidence that SH2B1β 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 SH2B1β out of focal adhesions. We also show that growth hormone (GH) increases cycling of SH2B1β into and out of focal adhesions. Ser161 and Ser165 in SH2B1β fall within consensus PKC substrate motifs. Mutating these two serine residues into alanine residues abrogates PMA-induced redistribution of SH2B1β out of focal adhesions, decreases SH2B1β 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 SH2B1β in focal adhesions and increases the number of focal adhesions per cell. These results suggest that activation of PKC regulates SH2B1β focal adhesion localization through phosphorylation of Ser161 and/or Ser165. The finding that phosphorylation of SH2B1β increases the number of focal adhesions suggests a mechanism for the stimulatory effect on cell motility of SH2B1β.
authors: University of Michigan Medical School, Ann Arbor, MI 48109-5622, USA.
authors: Nathan J
authors: NJ
authors: Lanning
authors: Hsiao-Wen
authors: HW
authors: Su
authors: Lawrence S
authors: LS
authors: Argetsinger
authors: Christin
authors: C
authors: Carter-Su
mesh_terms: D000199:Actins / Q000378:metabolism; D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D015815:Cell Adhesion Molecules / Q000235:genetics / Q000378:metabolism*; D002460:Cell Line; D002465:Cell Movement; D003599:Cytoskeleton / Q000378:metabolism; D022001:Focal Adhesions / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D013006:Growth Hormone / Q000494:pharmacology; D051379:Mice; D016297:Mutagenesis, Site-Directed; D009154:Mutation / Q000235:genetics; D010766:Phosphorylation / Q000187:drug effects; D021381:Protein Transport / Q000187:drug effects; D012694:Serine / Q000235:genetics; D015398:Signal Transduction / Q000187:drug effects; D015219:Substrate Cycling / Q000187:drug effects; D013755:Tetradecanoylphorbol Acetate / Q000031:analogs & derivatives / Q000378:metabolism
chemical_list: D000199:Actins; D048868:Adaptor Proteins, Signal Transducing; D015815:Cell Adhesion Molecules; C518910:SH2B1 protein, human; D012694:Serine; C020922:4-O-methyl-12-O-tetradecanoylphorbol 13-acetate; D013006:Growth Hormone; D013755:Tetradecanoylphorbol Acetate