Identification of SH2B1β as a focal adhesion protein that regulates focal adhesion size and number
Year: 2011
Type: article
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.
Source: Journal of Cell Science
DOI: 10.1242/jcs.081547
Institutions: University of Michigan, Michigan Medicine
Language: English
Subfield: Immunology and Allergy
Field: Medicine
Domain: Health Sciences
Open Access status: bronze
Funders: University of Michigan, National Institutes of Health, University of Michigan Comprehensive Cancer Center, National Cancer Institute, National Institute of General Medical Sciences, National Institute of Diabetes and Digestive and Kidney Diseases, National Institute of Arthritis and Musculoskeletal and Skin Diseases, Eunice Kennedy Shriver National Institute of Child Health and Human Development
Awards: G1266416359, G2165934530, Michigan Diabetes Research and Training Center, Cellular mechanism of action of SH2B1 isoforms implicated in human obesity, ARTHRITIS AND MUSCULOSKELETAL DISEASES CENTER, Cellular and Molecular Biology at Michigan, Training Program in Organogenesis, G7158048039, G9000163722, G9000265101, G9000301458, University of Michigan Rogel Cancer Center Support Grant 2023-2028, Michigan Diabetes Research Center (MDRC)
OpenAlex ID: W1974838076