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Involvement of JAK2 and Src kinase tyrosine phosphorylation in human growth hormone-stimulated increases in cytosolic free Ca2+ and insulin secretion.

Authors: Zhang, F  Zhang, Q  Tengholm, A  Sjoholm, A 
Citation: Zhang F, etal., Am J Physiol Cell Physiol. 2006 Sep;291(3):C466-75. Epub 2006 Apr 5.
Pubmed: (View Article at PubMed) PMID:16597920
DOI: Full-text: DOI:10.1152/ajpcell.00418.2005

We previously reported that human growth hormone (hGH) increases cytoplasmic Ca(2+) concentration ([Ca(2+)](i)) and proliferation in pancreatic beta-cells (Sjoholm A, Zhang Q, Welsh N, Hansson A, Larsson O, Tally M, and Berggren PO. J Biol Chem 275: 21033-21040, 2000) and that the hGH-induced rise in [Ca(2+)](i) involves Ca(2+)-induced Ca(2+) release facilitated by tyrosine phosphorylation of ryanodine receptors (Zhang Q, Kohler M, Yang SN, Zhang F, Larsson O, and Berggren PO. Mol Endocrinol 18: 1658-1669, 2004). Here we investigated the tyrosine kinases that convey the hGH-induced rise in [Ca(2+)](i) and insulin release in BRIN-BD11 beta-cells. hGH caused tyrosine phosphorylation of Janus kinase (JAK)2 and c-Src, events inhibited by the JAK2 inhibitor AG490 or the Src kinase inhibitor PP2. Although hGH-stimulated rises in [Ca(2+)](i) and insulin secretion were completely abolished by AG490 and JAK2 inhibitor II, the inhibitors had no effect on insulin secretion stimulated by a high K(+) concentration. Similarly, Src kinase inhibitor-1 and PP2, but not its inactive analog PP3, suppressed [Ca(2+)](i) elevation and completely abolished insulin secretion stimulated by hGH but did not affect responses to K(+). Ovine prolactin increased [Ca(2+)](i) and insulin secretion to a similar extent as hGH, effects prevented by the JAK2 and Src kinase inhibitors. In contrast, bovine GH evoked a rise in [Ca(2+)](i) but did not stimulate insulin secretion. Neither JAK2 nor Src kinase inhibitors influenced the effect of bovine GH on [Ca(2+)](i). Our study indicates that hGH stimulates rise in [Ca(2+)](i) and insulin secretion mainly through activation of the prolactin receptor and JAK2 and Src kinases in rat insulin-secreting cells.


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CRRD Object Information
CRRD ID: 1641815
Created: 2007-08-22
Species: All species
Last Modified: 2007-08-22
Status: ACTIVE


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