| http://purl.uniprot.org/citations/22669945 | http://www.w3.org/1999/02/22-rdf-syntax-ns#type | http://purl.uniprot.org/core/Journal_Citation |
| http://purl.uniprot.org/citations/22669945 | http://www.w3.org/1999/02/22-rdf-syntax-ns#type | http://purl.uniprot.org/core/Journal_Citation |
| http://purl.uniprot.org/citations/22669945 | http://www.w3.org/2000/01/rdf-schema#comment | "The p21-activated kinase-1 (PAK1) is implicated in regulation of insulin exocytosis as an effector of Rho GTPases. PAK1 is activated by the onset of glucose-stimulated insulin secretion (GSIS) through phosphorylation of Thr-423, a major activation site by Cdc42 and Rac1. However, the kinase(s) that phosphorylates PAK1 at Thr-423 in islet β-cells remains elusive. The present studies identified SAD-A (synapses of amphids defective), a member of AMP-activated protein kinase-related kinases exclusively expressed in brain and pancreas, as a key regulator of GSIS through activation of PAK1. We show that SAD-A directly binds to PAK1 through its kinase domain. The interaction is mediated by the p21-binding domain (PBD) of PAK1 and requires both kinases in an active conformation. The binding leads to direct phosphorylation of PAK1 at Thr-423 by SAD-A, triggering the onset of GSIS from islet β-cells. Consequently, ablation of PAK1 kinase activity or depletion of PAK1 expression completely abolishes the potentiating effect of SAD-A on GSIS. Consistent with its role in regulating GSIS, overexpression of SAD-A in MIN6 islet β-cells significantly stimulated cytoskeletal remodeling, which is required for insulin exocytosis. Together, the present studies identified a critical role of SAD-A in the activation of PAK1 during the onset of insulin exocytosis."xsd:string |
| http://purl.uniprot.org/citations/22669945 | http://purl.org/dc/terms/identifier | "doi:10.1074/jbc.m112.378372"xsd:string |
| http://purl.uniprot.org/citations/22669945 | http://purl.org/dc/terms/identifier | "doi:10.1074/jbc.m112.378372"xsd:string |
| http://purl.uniprot.org/citations/22669945 | http://purl.uniprot.org/core/author | "Han X."xsd:string |
| http://purl.uniprot.org/citations/22669945 | http://purl.uniprot.org/core/author | "Han X."xsd:string |
| http://purl.uniprot.org/citations/22669945 | http://purl.uniprot.org/core/author | "Li J."xsd:string |
| http://purl.uniprot.org/citations/22669945 | http://purl.uniprot.org/core/author | "Li J."xsd:string |
| http://purl.uniprot.org/citations/22669945 | http://purl.uniprot.org/core/author | "Liang Q."xsd:string |
| http://purl.uniprot.org/citations/22669945 | http://purl.uniprot.org/core/author | "Liang Q."xsd:string |
| http://purl.uniprot.org/citations/22669945 | http://purl.uniprot.org/core/author | "Shi Y."xsd:string |
| http://purl.uniprot.org/citations/22669945 | http://purl.uniprot.org/core/author | "Shi Y."xsd:string |
| http://purl.uniprot.org/citations/22669945 | http://purl.uniprot.org/core/author | "Sun C."xsd:string |
| http://purl.uniprot.org/citations/22669945 | http://purl.uniprot.org/core/author | "Sun C."xsd:string |
| http://purl.uniprot.org/citations/22669945 | http://purl.uniprot.org/core/author | "Yang W."xsd:string |
| http://purl.uniprot.org/citations/22669945 | http://purl.uniprot.org/core/author | "Yang W."xsd:string |
| http://purl.uniprot.org/citations/22669945 | http://purl.uniprot.org/core/author | "Ye G."xsd:string |
| http://purl.uniprot.org/citations/22669945 | http://purl.uniprot.org/core/author | "Ye G."xsd:string |
| http://purl.uniprot.org/citations/22669945 | http://purl.uniprot.org/core/author | "Chang Z."xsd:string |
| http://purl.uniprot.org/citations/22669945 | http://purl.uniprot.org/core/author | "Chang Z."xsd:string |
| http://purl.uniprot.org/citations/22669945 | http://purl.uniprot.org/core/author | "Nie J."xsd:string |
| http://purl.uniprot.org/citations/22669945 | http://purl.uniprot.org/core/author | "Nie J."xsd:string |
| http://purl.uniprot.org/citations/22669945 | http://purl.uniprot.org/core/author | "Faruque O."xsd:string |
| http://purl.uniprot.org/citations/22669945 | http://purl.uniprot.org/core/author | "Faruque O."xsd:string |