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• W2024853260 endingPage "11487" @default.
• W2024853260 startingPage "11476" @default.
• W2024853260 abstract "Second-phase insulin secretion sustains insulin release in the face of hyperglycemia associated with insulin resistance, requiring the continued mobilization of insulin secretory granules to the plasma membrane. Cdc42, the small Rho family GTPase recognized as the proximal glucose-specific trigger to elicit second-phase insulin secretion, signals downstream to activate the p21-activated kinase (PAK1), which then signals to Raf-1/MEK/ERK to induce filamentous actin (F-actin) remodeling, to ultimately mobilize insulin granules to the plasma membrane. However, the steps required to initiate Cdc42 activation in a glucose-specific manner in β cells have remained elusive. Toward this, we identified the involvement of the Src family kinases (SFKs), based upon the ability of SFK inhibitors to block glucose-stimulated Cdc42 and PAK1 activation events as well as the amplifying pathway of glucose-stimulated insulin release, in MIN6 β cells. Indeed, subsequent studies performed in human islets revealed that SFK phosphorylation was induced only by glucose and within 1 min of stimulation before the activation of Cdc42 at 3 min. Furthermore, pervanadate treatment validated the phosphorylation event to be tyrosine-specific. Although RT-PCR showed β cells to express five different SFK proteins, only two of these, YES and Fyn kinases, were found localized to the plasma membrane, and of these two, only YES kinase underwent glucose-stimulated tyrosine phosphorylation. Immunodetection and RNAi analyses further established YES kinase as a proximal glucose-specific signal in the Cdc42-signaling cascade. Identification of YES kinase provides new insight into the mechanisms underlying the sustainment of insulin secretion via granule mobilization/replenishment and F-actin remodeling." @default.
• W2024853260 created "2016-06-24" @default.
• W2024853260 creator A5016699391 @default.
• W2024853260 creator A5028036646 @default.
• W2024853260 creator A5045317949 @default.
• W2024853260 creator A5061103665 @default.
• W2024853260 date "2014-04-01" @default.
• W2024853260 modified "2023-10-18" @default.
• W2024853260 title "YES, a Src Family Kinase, Is a Proximal Glucose-specific Activator of Cell Division Cycle Control Protein 42 (Cdc42) in Pancreatic Islet β Cells" @default.
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• W2024853260 doi "https://doi.org/10.1074/jbc.m114.559328" @default.
• W2024853260 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/4036283" @default.
• W2024853260 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/24610809" @default.
• W2024853260 hasPublicationYear "2014" @default.
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