RGD Reference Report - Involvement of JAK2 and Src kinase tyrosine phosphorylation in human growth hormone-stimulated increases in cytosolic free Ca2+ and insulin secretion. - Rat Genome Database

RGD Reference Report - Involvement of JAK2 and Src kinase tyrosine phosphorylation in human growth hormone-stimulated increases in cytosolic free Ca2+ and insulin secretion. - Rat Genome Database

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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.
RGD ID:	1641815
Pubmed:	PMID:16597920 (View Abstract at PubMed)
DOI:	DOI:10.1152/ajpcell.00418.2005 (Journal Full-text)
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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Term	Qualifier	Evidence	With	Reference	Notes	Source	Original Reference(s)
positive regulation of cytosolic calcium ion concentration		IMP		1641815	in response to human growth hormone	RGD
positive regulation of insulin secretion		IMP		1641815	in response to human growth hormone	RGD

Objects Annotated

Genes (Rattus norvegicus)

Jak2 (Janus kinase 2)

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