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.
James L. Clements, Jong Ran Lee, Barbara Gross, Baoli Yang, John D. Olson, Alexander Sandra, Stephen P. Watson, Steven R. Lentz, Gary A. Koretzky
Title and authors | Publication | Year |
---|---|---|
Blood flow reprograms lymphatic vessels to blood vessels through shear-mediated loss of endothelial PROX1
Chiu-Yu Chen, Cara Bertozzi, Zhiying Zou, Lijun Yuan, John Lee, Min Min Lu, Stanley Stachelek, Sathish Srinivasan, Lili Guo, Andres Vicente, Patricia Mericko, Robert J. Levy, Taija Makinen, Guillermo Oliver, Mark Kahn |
Journal of Clinical Investigation | 2012 |
Antiplatelet Agents
P Gresele, GV Born, C Patrono, CP Page |
2012 | |
Crucial role of SLP-76 and ADAP for neutrophil recruitment in mouse kidney ischemia-reperfusion injury
H Block, JM Herter, J Rossaint, A Stadtmann, S Kliche, CA Lowell, A Zarbock |
Journal of Experimental Medicine | 2012 |
Blood flow reprograms lymphatic vessels to blood vessels
CY Chen, C Bertozzi, Z Zou, L Yuan, JS Lee, MM Lu, SJ Stachelek, S Srinivasan, L Guo, A Vicente, A Vincente, P Mericko, RJ Levy, T Makinen, G Oliver, ML Kahn |
Journal of Clinical Investigation | 2012 |
Platelet CLEC-2 and podoplanin in cancer metastasis
KL Lowe, L Navarro-Nunez, SP Watson |
Thrombosis Research | 2012 |