These tools will no longer be maintained as of December 31, 2024. Archived website can be found here. PubMed4Hh GitHub repository can be found here. Contact NLM Customer Service if you have questions.


Pubmed for Handhelds

PUBMED FOR HANDHELDS

Search MEDLINE/PubMed

  • Title: Adapter protein SH2B1beta cross-links actin filaments and regulates actin cytoskeleton.
    Author: Rider L, Tao J, Snyder S, Brinley B, Lu J, Diakonova M.
    Journal: Mol Endocrinol; 2009 Jul; 23(7):1065-76. PubMed ID: 19342444.
    Abstract:
    The Src homology 2 (SH2) domain-containing adapter protein SH2B1beta plays a role in severe obesity, leptin and insulin resistance, and infertility. SH2B1beta was initially identified as a Janus tyrosine kinase 2 (JAK2) substrate, and it has been implicated in cell motility and regulation of the actin rearrangement in response to GH and platelet-derived growth factor. SH2B1beta is also required for maximal actin-based motility of Listeria. Here we have used a low-speed pelleting assay and electron microscopy to demonstrate that SH2B1beta has two actin-binding sites and that it cross-links actin filaments in vitro. Wild-type SH2B1beta localized to cell ruffles and along filopodia, but deletion of amino acids 150-200 (the first actin-binding site) led to mislocalization of the protein to filopodia tip complexes where it colocalized with vasodilator-stimulated phosphoprotein (VASP). Based on studies performed in VASP-deficient MVD7(-/-) cells, with or without green fluorescent protein-VASP reconstitution, we concluded that the proper intracellular localization of native SH2B1beta required the presence of the first SH2B1beta actin-binding site and VASP. Finally, we found that both SH2B1beta actin-binding domains were required for maximal GH- and prolactin-induced cell ruffling. Together, these results suggest that SH2B1beta functions as an adapter protein that cross-links actin filaments, leading to modulation of cellular responses in response to JAK2 activation.
    [Abstract] [Full Text] [Related] [New Search]