The B cell antigen receptor (BCR) consists of the membrane-bound immunoglobulin (mlg) crosslinking, yet the pattern of protein phosphorylation is similar to that observed after BCR stimulation by antigen. The response requires cellular integrity because tyrosine phosphorylation of most substrates is not visible in cell lysates. Cells that express a BCR containing an Ig-a subunit with a mutated immunoreceptor tyrosine-based activation motif display a delayed response. The data suggest that, once expressed on the surface, the BCR organizes protein tyrosine phosphatases, PTKs, and their substrates into a transducer complex that can be activated by pervanadate/H202 in the absence of BCR crosslinking. Assembly of this preformed complex seems to be a prerequisite for BCR-mediated signal transduction.The B cell antigen receptor (BCR) is composed of multiple subunits. Antigen bound by transmembrane immunoglobulins (mIg) of different classes transmits an activation signal to the cell interior through the mlg-associated Ig-a/Ig-f3 heterodimer (1, 2). The immunoreceptor tyrosine-based activation motif (ITAM) (3) plays a critical role in this process and is responsible for the communication of the BCR with cytoplasmic protein tyrosine kinases (PTKs) (4-8). The amino acid sequence of ITAM is DEx6D/ExxYxxLx7YXXI/L and a single copy of the motif is present in the cytoplasmic part of both Ig-a and Ig-13. The current model of BCR signaling predicts that crosslinking of the BCR results in activation of the Src-related

Lymphocytes respond to antigen receptor engagement with tyrosine phosphorylation of many cellular proteins, some of which have been identified and functionally characterized. Here we describe SH3P7, a novel substrate protein for Src and Syk family kinases. SH3P7 migrates in sodium dodecyl sulfate-polyacrylamide gel electrophoresis as a 55-kDa protein that is preferentially expressed in brain, thymus, and spleen. It contains multiple amino acid sequence motifs, including two consensus tyrosine phosphorylation sites of the YXXP type and one SH3 domain. A region of sequence similarity, which we named SCAD, was found in SH3P7 and three actin-binding proteins. The SCAD region may represent a new type of protein-protein interaction domain that mediates binding to actin. Consistent with this possibility, SH3P7 colocalizes with actin filaments of the cytoskeleton. Altogether, our data implicate SH3P7 as an adapter protein which links antigen receptor signaling to components of the cytoskeleton.