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Blood, 3 September 2009, Vol. 114, No. 10, pp. 2193-2196. Prepublished online as a Blood First Edition Paper on June 10, 2009; DOI 10.1182/blood-2009-03-208074. This Article Full Text Full Text (PDF) Supplemental Figure All Versions of this Article: blood-2009-03-208074v1 114/10/2193    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 Google Scholar Articles by Canobbio, I. Articles by Torti, M. PubMed PubMed Citation Articles by Canobbio, I. Articles by Torti, M. Related Collections Platelets and Thrombopoiesis Brief Reports Related Article in Blood Online Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  PLATELETS AND THROMBOPOIESIS Brief report Genetic evidence for a predominant role of PI3Kβ catalytic activity in ITAM- and integrin-mediated signaling in platelets Ilaria Canobbio1,*, Lucia Stefanini1,*, Lina Cipolla1, Elisa Ciraolo2, Cristian Gruppi1, Cesare Balduini1, Emilio Hirsch2,, and Mauro Torti1, 1 Department of Biochemistry, University of Pavia, Pavia; and 2 Molecular Biotechnology Center, Department of Genetics, Biology and Biochemistry, University of Turin, Turin, Italy Phosphatidylinositol 3-kinase (PI3K) isoforms PI3Kβ and PI3K are implicated in platelet adhesion, activation, and aggregation, but their relative contribution is still unclear or controversial. Here, we report the first comparative functional analysis of platelets from mice expressing a catalytically inactive form of PI3Kβ or PI3K. We demonstrate that both isoforms were similarly required for maximal activation of the small GTPase Rap1b and for complete platelet aggregation upon stimulation of G protein–coupled receptors for adenosine 5'-diphosphate (ADP) or U46619. [GenBank] Their contribution to these events, however, was largely redundant and dispensable. However, PI3Kβ, but not PI3K, enzymatic activity was absolutely required for Akt phosphorylation, Rap1 activation, and platelet aggregation downstream of the immunoreceptor tyrosine-based activation motif (ITAM)–bearing receptor glycoprotein VI (GPVI). Moreover, PI3Kβ was a major essential regulator of platelet adhesion to fibrinogen and of integrin IIbβ3-mediated spreading. These results provide genetic evidence for a crucial and selective role of PI3Kβ in signaling through GPVI and integrin IIbβ3. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? Related Article in Blood Online: PI3Kβ goes to the head of its class Debra K. Newman Blood 2009 114: 2011-2012. [Abstract] [Full Text] [PDF] This article has been cited by other articles: D. K. Newman PI3K{beta} goes to the head of its class Blood, September 3, 2009; 114(10): 2011 - 2012. [Abstract] [Full Text] [PDF]

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