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Blood, 15 December 2007, Vol. 110, No. 13, pp. 4206-4213. Prepublished online as a Blood First Edition Paper on September 7, 2007; DOI 10.1182/blood-2007-03-080804. This Article Full Text Full Text (PDF) All Versions of this Article: blood-2007-03-080804v1 110/13/4206    most recent Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Rights and Permissions Citing Articles Citing Articles via HighWire Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Kim, S. Articles by Kunapuli, S. P. Search for Related Content PubMed PubMed Citation Articles by Kim, S. Articles by Kunapuli, S. P. Related Collections Hemostasis, Thrombosis, and Vascular Biology Signal Transduction Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  HEMOSTASIS, THROMBOSIS, AND VASCULAR BIOLOGY Insulin-like growth factor-1 regulates platelet activation through PI3-K isoform Soochong Kim1, Analia Garcia1, Shaun P. Jackson2, and Satya P. Kunapuli1 1 Department of Physiology and Pharmacology and the Sol Sherry Thrombosis Research Center, Temple University School of Medicine, Philadelphia, PA; and 2 Australian Centre for Blood Diseases, Monash University, Victoria, Australia Platelets release insulin-like growth factor-1 (IGF-1) from granules upon activation. We have investigated the regulation of IGF-1 in Gi-dependent pathways leading to Akt activation and the role of IGF-1 in platelet activation. IGF-1 alone failed to induce platelet aggregation, but IGF-1 potentiated 2-MeSADP–induced platelet aggregation in a concentration-dependent manner. IGF-1 triggered platelet aggregation in combination with selective P2Y1 receptor activation. IGF-1 also caused platelet aggregation without shape change when combined with selective Gz stimulation by epinephrine, suggesting the role of IGF-1 in platelet aggregation by supplementing Gi pathways. The potentiating effect of IGF-1 was not affected by intracellular calcium chelation. Importantly, IGF-1 was unable to potentiate platelet aggregation by the phosphatidylinositol 3-kinase (PI3-K) inhibitor wortmannin, suggesting a critical regulation by PI3-K. Moreover, the potentiating effect of IGF-1 was abolished by the presence of PI3-K p110 inhibitor PIK-75. Stimulation of platelets with IGF-1 resulted in phosphorylation of Akt, a downstream effector of PI3-K, which was completely inhibited by wortmannin. IGF-1-induced Akt phosphorylation was abolished by PIK-75 suggesting the contribution of PI3-K p110 for activation of Akt by IGF-1. These results demonstrate that IGF-1 plays a role in potentiating platelet aggregation by complementing Gi- but not Gq-signaling pathways via PI3-K p110. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: F. Morello, A. Perino, and E. Hirsch Phosphoinositide 3-kinase signalling in the vascular system Cardiovasc Res, May 1, 2009; 82(2): 261 - 271. [Abstract] [Full Text] [PDF]

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