Fetal hemorrhage and platelet dysfunction in SLP-76-deficient mice

James L. Clements, Jong Ran Lee, Barbara Gross, Baoli Yang, John D Olson, Alexander Sandra, Stephen P. Watson, Steven R. Lentz, Gary A. Koretzky

Research output: Contribution to journalArticle

149 Citations (Scopus)

Abstract

The adapter protein SLP-76 is expressed in T lymphocytes and hematopoietic cells of the myeloid lineage, and is known to be a substrate of the protein tyrosine kinases that are activated after ligation of the T-cell antigen receptor. Transient overexpression of SLP-76 in a T-cell line potentiates transcriptional activation after T-cell receptor ligation, while loss of SLP-76 expression abrogates several T-cell receptor-dependent signaling pathways. Mutant mice that lack SLP-76 manifest a severe block at an early stage of thymocyte development, implicating SLP-76 in signaling events that promote thymocyte maturation. While it is clear that SLP-76 plays a key role in development and activation of T lymphocytes, relatively little is understood regarding its role in transducing signals initiated after receptor ligation in other hematopoietic cell types. In this report, we describe fetal hemorrhage and perinatal mortality in SLP-76-deficient mice. Although megakaryocyte and platelet development proceeds normally in the absence of SLP-76, collagen-induced platelet aggregation and granule release is markedly impaired. Furthermore, treatment of SLP-76-deficient platelets with collagen fails to elicit tyrosine phosphorylation of phospholipase C- γ2 (PLC-γ2), suggesting that SLP-76 functions upstream of PLC-γ2 activation. These data provide one potential mechanism for the fetal hemorrhage observed in SLP-76-deficient mice and reveal that SLP-76 expression is required for optimal receptor-mediated signal transduction in platelets as well as T lymphocytes.

Original languageEnglish (US)
Pages (from-to)19-25
Number of pages7
JournalJournal of Clinical Investigation
Volume103
Issue number1
StatePublished - Jan 1999
Externally publishedYes

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Blood Platelets
T-Cell Antigen Receptor
Hemorrhage
Ligation
T-Lymphocytes
Type C Phospholipases
Thymocytes
Collagen
Fetal Mortality
Megakaryocytes
Perinatal Mortality
Cell Lineage
Platelet Aggregation
Protein-Tyrosine Kinases
Transcriptional Activation
Tyrosine
Signal Transduction
Phosphorylation
Cell Line
Proteins

ASJC Scopus subject areas

  • Medicine(all)

Cite this

Clements, J. L., Lee, J. R., Gross, B., Yang, B., Olson, J. D., Sandra, A., ... Koretzky, G. A. (1999). Fetal hemorrhage and platelet dysfunction in SLP-76-deficient mice. Journal of Clinical Investigation, 103(1), 19-25.

Fetal hemorrhage and platelet dysfunction in SLP-76-deficient mice. / Clements, James L.; Lee, Jong Ran; Gross, Barbara; Yang, Baoli; Olson, John D; Sandra, Alexander; Watson, Stephen P.; Lentz, Steven R.; Koretzky, Gary A.

In: Journal of Clinical Investigation, Vol. 103, No. 1, 01.1999, p. 19-25.

Research output: Contribution to journalArticle

Clements, JL, Lee, JR, Gross, B, Yang, B, Olson, JD, Sandra, A, Watson, SP, Lentz, SR & Koretzky, GA 1999, 'Fetal hemorrhage and platelet dysfunction in SLP-76-deficient mice', Journal of Clinical Investigation, vol. 103, no. 1, pp. 19-25.
Clements JL, Lee JR, Gross B, Yang B, Olson JD, Sandra A et al. Fetal hemorrhage and platelet dysfunction in SLP-76-deficient mice. Journal of Clinical Investigation. 1999 Jan;103(1):19-25.
Clements, James L. ; Lee, Jong Ran ; Gross, Barbara ; Yang, Baoli ; Olson, John D ; Sandra, Alexander ; Watson, Stephen P. ; Lentz, Steven R. ; Koretzky, Gary A. / Fetal hemorrhage and platelet dysfunction in SLP-76-deficient mice. In: Journal of Clinical Investigation. 1999 ; Vol. 103, No. 1. pp. 19-25.
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