tailieunhanh - báo cáo khoa hoc : The regulation of N-methyl-D-aspartate receptors by Src kinase

Src family kinases (SFKs) play critical roles in the regulation of many cellular functions by growth factors, G-protein-coupled receptors and ligand-gated ion channels. Recent data have shown that SFKs serve as a convergent point of multiple signaling pathways regulating N-methyl-D-aspartate (NMDA) receptors in the central nervous system. | IFEBS Journal MINIREVIEW The regulation of N-methyl-D-aspartate receptors by Src kinase Bradley R. Groveman1 Shuang Feng1 2 Xiao-Qian Fang1 Melissa Pflueger1 Shuang-Xiu Lin1 Ewa A. Bienkiewicz1 and XianMin Yu1 1 Department of BiomedicalSciences Florida State University Tallahassee FL USA 2 Department of Otolaryngology-Head and Neck Surgery First Affiliated Hospital Guangxi MedicalUniversity Nanning China Keywords NMDA receptors protein unfolding PTPa and Csk Src family kinases the SH2 and SH3 domains Correspondence B. R. Groveman Department of Biomedical Sciences Florida State University Tallahassee FL 32306 USA Fax 1 406 363 9286 Tel 1 406 363 9341 E-mail Present address Laboratory of Persistent Viral Diseases LPVD Rocky Mountain Laboratories RML NationalInstitute of Allergy and Infectious Diseases NIAID National Institutes of Health NIH Received 31 May 2011 revised 29 October 2011 accepted 1 November 2011 doi Src family kinases SFKs play critical roles in the regulation of many cellular functions by growth factors G-protein-coupled receptors and ligand-gated ion channels. Recent data have shown that SFKs serve as a convergent point of multiple signaling pathways regulating N-methyl-D-aspartate NMDA receptors in the central nervous system. Multiple SFK molecules such as Src and Fyn closely associate with their substrate NMDA receptors via indirect and direct binding mechanisms. The NMDA receptor is associated with an SFK signaling complex consisting of SFKs the SFK-activating phosphatase protein tyrosine phosphatase a and the SFK-inactivating kinase C-terminal Src kinase. Early studies have demonstrated that intramolecular interactions with the SH2 or SH3 domain lock SFKs in a closed conformation. Disruption of the interdomain interactions can induce the activation of SFKs with multiple signaling pathways involved in regulation of this process. The enzyme activity of SFKs appears graded exhibiting different