34 research outputs found
Small intestinal submucosa-derived extracellular matrix bioscaffold significantly enhances angiogenic factor secretion from human mesenchymal stromal cells
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Divergent and convergent signaling by the diacylglycerol second messenger pathway in mammals
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Biochemical Characterization of Hyperactive β2-Chimaerin Mutants Revealed an Enhanced Exposure of C1 and Rac-GAP Domains
No full textDifferential ability of MSCs isolated from placenta and cord as feeders for supporting ex vivo expansion of umbilical cord blood derived CD34+ cells
No full textComparative analysis of mesenchymal stem cells derived from amniotic membrane, umbilical cord, and chorionic plate under serum-free condition
No full textCoordinated activation of the Rac-GAP β2-chimaerin by an atypical proline-rich domain and diacylglycerol
No full textChimaerins, a family of GTPase activating proteins (GAPs) for the small G-protein Rac, have been implicated in development, neuritogenesis, and cancer. These Rac-GAPs are regulated by the lipid second messenger diacylglycerol (DAG) generated by tyrosine-kinases such as the epidermal growth factor receptor (EGFR). Here we identify an atypical Pro-rich motif in chimaerins that binds to the adaptor protein Nck1. Unlike most Nck1 partners, chimaerins bind to the third SH3 domain of Nck1. This association is mediated by electrostatic interactions of basic residues within the Pro-rich motif with acidic clusters in the SH3 domain. EGF promotes the binding of β2-chimaerin to Nck1 in the cell periphery in a DAG-dependent manner. Moreover, β2-chimaerin translocation to the plasma membrane and its peripheral association with Rac1 requires Nck1. Our studies underscore a coordinated mechanism for β2-chimaerin activation that involves lipid interactions via the C1 domain and protein-protein interactions via the N-terminal Pro-rich region
