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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
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Cell Biology.
2006 (English)In: American Journal of Physiology - Cell Physiology, ISSN 0363-6143, E-ISSN 1522-1563, Vol. 291, no 3, C466-C475 p.Article in journal (Refereed) Published
Abstract [en]

We previously reported that human growth hormone (hGH) increases cytoplasmic Ca2+ concentration ([Ca2+](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 [Ca2+](i) involves Ca2+-induced Ca2+ 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 [Ca2+](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 [Ca2+](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 [Ca2+](i) elevation and completely abolished insulin secretion stimulated by hGH but did not affect responses to K+. Ovine prolactin increased [Ca2+](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 [Ca2+](i) but did not stimulate insulin secretion. Neither JAK2 nor Src kinase inhibitors influenced the effect of bovine GH on [Ca2+](i). Our study indicates that hGH stimulates rise in [Ca2+](i) and insulin secretion mainly through activation of the prolactin receptor and JAK2 and Src kinases in rat insulin-secreting cells.

Place, publisher, year, edition, pages
2006. Vol. 291, no 3, C466-C475 p.
Keyword [en]
c-Src, growth hormone receptor, prolactin receptor, Ca2+-induced, Ca2+ release
National Category
Medical and Health Sciences
URN: urn:nbn:se:uu:diva-22883DOI: 10.1152/ajpcell.00418.2005ISI: 000239627500008PubMedID: 16597920OAI: oai:DiVA.org:uu-22883DiVA: diva2:50656
Available from: 2007-03-06 Created: 2007-03-06 Last updated: 2011-06-28Bibliographically approved

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