Sci. STKE, 8 March 2005
T CELL ACTIVATION No Interaction Required
Activation of phospholipase C-1 (PLC-1), a critical early step in T cell activation through the T cell antigen receptor (TCR), is regulated by a complex of hematopoietic-specific adaptor proteins that includes SLP-76 (SH2 domain-containing leukocyte protein of 76 kD). P-I, a proline-rich 67-amino acid region of SLP-76 that binds to the SH3 domain of PLC-1 (SH3PLC), is required for TCR-mediated activation of PLC-1. Gonen et al. expressed deletion mutants of SLP-76 in an SLP-76-deficient cell line and discovered that, whereas complete deletion of P-I attenuated TCR-induced PLC-1 tyrosine phosphorylation and downstream sequelae of PLC-1 activation (calcium flux and NFAT activation), this did not depend on any particular portion of P-I. Further, SLP-76 functionality did not depend on its ability to bind SH3PLC. Indeed, a mutant in which the SH3PLC-binding region was deleted and the remaining amino acid sequence of P-I was scrambled to disrupt any other protein-binding domains retained the ability to mediate NFAT activation. Thus, the authors conclude that function of the P-I region may be independent of any protein-protein interactions and that this region may instead serve a structural role, perhaps as a spacer or a hinge.
R. Gonen, D. Beach, C. Ainey, D. Yablonski, T cell receptor-induced activation of phospholipase C-1 depends on a sequence-independent function of the P-I region of SLP-76. J. Biol. Chem. 280, 8364-8370 (2005). [Abstract] [Full Text]
Citation: No Interaction Required. Sci. STKE 2005, tw85 (2005).
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