CLONING AND CHARACTERIZATION OF APS, AN ADAPTER MOLECULE CONTAINING PH AND SH2 DOMAINS THAT IS TYROSINE-PHOSPHORYLATED UPON B-CELL RECEPTORSTIMULATION

Stimulation of B lymphocytes through their antigen receptor (BCR) resu lts in rapid increases in tyrosine phosphorylation of a number of prot eins, which leads to a cascade of biochemical changes that initiates B cell proliferation and differentiation or growth inhibition, A novel cDNA, designed APS, encoding an adaptor protein with a Pleckstrin homo logy (PH) domain, Src homology 2 (SH2) domain, and a tyrosine phosphor ylation site was cloned from a B cell cDNA library using a yeast two h ybrid system, APS is structurally similar to SH2-B, an SH2 protein tha t potentially binds to the immunoreceptor tyrosine-based activation mo tif (ITAM) as well as Lnk which is postulated to be a signal transduce r that Links T-cell receptor to phospholipase C gamma, Grb2 and phosph atidylinositol 3-kinase, APS expressed only in human Burkitt's lymphom a cells among cell Lines me examined and tyrosine phosphorylated in re sponse to BCR stimulation, APS bound to Shc irrespective of stimulatio n and bound to Grb2 after stimulation, suggesting that it plays a role in Linkage from BCR to Shc/Grb2 pathway, These results indicate that APS, SH2-B and Lnk form a new adaptor family that links immune recepto rs to signaling pathways involved in tyrosine-phosphorylation.