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Fetal hemorrhage and platelet dysfunction in SLP-76-deficient mice.
The Journal of clinical investigation
  • J. L. Clements
  • J. R. Lee
  • B. Gross
  • Baoli Yang, University of Iowa
  • J. D. Olson
  • A. Sandra
  • S. P. Watson
  • S. R. Lentz
  • G. A. Koretzky
Document Type
Peer Reviewed
Publication Date
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-gamma2 (PLC-gamma2), suggesting that SLP-76 functions upstream of PLC-gamma2 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.
  • Adaptor Proteins,
  • Signal Transducing,
  • Animals,
  • Blood Platelets,
  • Bone Marrow Cells,
  • Collagen,
  • Enzyme Precursors,
  • Fetus,
  • Hemorrhage,
  • Histocytochemistry,
  • Intracellular Signaling Peptides and Proteins,
  • Isoenzymes,
  • Megakaryocytes,
  • Mice,
  • Mice,
  • Knockout,
  • Phospholipase C gamma,
  • Phosphoproteins,
  • Phosphorylation,
  • Phosphotyrosine,
  • Platelet Aggregation,
  • Protein-Tyrosine Kinases,
  • Receptors,
  • Cell Surface,
  • Signal Transduction,
  • T-Lymphocytes,
  • Type C Phospholipases
Published Article/Book Citation
The Journal of clinical investigation (1999) 103:1, pp. 19-25.
Citation Information
J. L. Clements, J. R. Lee, B. Gross, Baoli Yang, et al.. "Fetal hemorrhage and platelet dysfunction in SLP-76-deficient mice." The Journal of clinical investigation Vol. 103 Iss. 1 (1999) p. 19 - 25 ISSN: 0021-9738
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