GrpL, a Grb2-related adaptor protein, interacts with SLP-76 to regulate nuclear factor of activated T cell activation

Propagation of signals from the T cell antigen receptor (TCR) involves a nu mber of adaptor molecules. SH2 domain-containing protein 76 (SLP-76) intera cts with the guanine nucleotide exchange factor Vav to activate the nuclear factor of activated cells (NF-AT), and its expression is required for norm al T cell development. We report the cloning and characterization of a nove l Grb2-like adaptor molecule designated as Grb2-related protein of the lymp hoid system (GrpL). Expression of GrpL is restricted to hematopoietic tissu es, and it is distinguished from Grb2 by having a proline-rich region. GrpL can be coimmunoprecipitated with SLP-76 but not with Sos1 or Sos2 from Jur kat cell lysates. In contrast, Grb2 can be coimmunoprecipitated with Sos1 a nd Sos2 but not with SLP-76. Moreover, tyrosine-phosphorylated LAT/pp36/38 in detergent lysates prepared from anti-CD3 stimulated T cells associated w ith Grb2 but not GrpL. These data reveal the presence of distinct complexes involving GrpL and Grb2 in T cells. A functional role of the GrpL-SLP-76 c omplex is suggested by the ability of GrpL to act alone or in concert with SLP-76 to augment NF-AT activation in Jurkat T cells.