Journal
BLOOD
Volume 102, Issue 10, Pages 3592-3599Publisher
AMER SOC HEMATOLOGY
DOI: 10.1182/blood-2003-04-1142
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The Tec family kinase Btk plays an important role in the regulation of phospholipase Cgamma2 (PLCgamma2) downstream of the collagen receptor glycoprotein VI (GPVI) in human platelets. Platelets also express a second member of this family, Tec; however, its function has not been analyzed. To address the role of Tec, we analyzed Btk(-/-), Tec(-/-), and Btk/Tec double-deficient (Btk(-/-)/Tec(-/-)) platelets. Tec(-/-) platelets exhibit a minor reduction in aggregation to threshold concentrations of collagen or the GPVI-specific agonist collagen-related peptide (CRP), whereas responses to higher concentrations are normal. Tyrosine phosphorylation of PLCgamma2 by collagen and CRP is not altered in Tec(-/-) platelets. However, Btk(-/-)/Tec(-/-) platelets exhibit a greater reduction in PLCgamma2 phosphorylation than is seen in the absence of Btk, thus revealing an important role for Tec in this situation. Furthermore, Btk(-/-)/Tec(-/-) platelets fall to undergo an increase in Ca2+, aggregation, secretion, and spreading in response to collagen or CRP, whereas they aggregate normally to adenosine diphosphate (ADP) and spread on fibrinogen. A residual GPVI signal exists in the Btk(-/-)/Tec(-/-) platelets as CRP synergizes with ADP to mediate aggregation. These results demonstrate an essential requirement for Tec and Btk in platelet activation by GPVI and reveal a functional role for Tec in the regulation of PLCgamma2 in the absence of Btk. (C) 2003 by The American Society of Hematology.
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