P150(TSP), CONSERVED NUCLEAR PHOSPHOPROTEIN THAT CONTAINS MULTIPLE TETRATRICOPEPTIDE REPEATS AND BINDS SPECIFICALLY TO SH2 DOMAINS

Src homology 2 (SH2) domains are structural modules that function in t he assembly of multicomponent signaling complexes by binding to specif ic phosphopeptides. The tetratricopeptide repeat (TPR) is a distinct s tructural motif that has been suggested to mediate protein-protein int eractions, Among SH2-binding phosphoproteins purified from the mouse B cell lymphoma A20, a 150-kDa species was identified and the correspon ding complementary DNA (cDNA) was molecularly cloned, This protein enc oded by this cDNA, which we have termed p150(TSP) (for TPR-containing, SH2-binding phosphoprotein), is located predominantly in the nucleus and is highly conserved in evolution, The gene encoding p150(TSP) (Tsp ) was mapped to chromosome 7 of the mouse with gene order: centromere- Tyr-Wnt11-Tsp-Zp2. The amino-terminal two-thirds of p150(TSP) consist almost entirely of tandemly arranged TPR units, which mediate specific , homotypic protein interactions in transfected cells. The carboxyl-te rminal third of p150(TSP) which is serine- and glutamic acid-rich, is essential for SH2 binding; this interaction is dependent on serine/thr eonine phosphorylation but independent of tyrosine phosphorylation, Th e sequence and binding properties of p150(TSP) suggest that it may med iate interactions between TPR-containing and SH2-containing proteins.