A putative modular domain present in diverse signaling proteins

Proteins involved in signal transduction consist of one or more modular domains. These modules can confer catalytic or structural functions or mediate protein-protein interactions. Src homology 3 (SH3) domains are presumed to mediate associations between signaling proteins (Mayer and Baltimore, 1993; Pawson and Gish, 1992), and several SH3-binding proteins have been isolated (Cicchetti et al., 1992). We have noticed that one of these SH3-binding proteins, termed 3BP2 (Cicchetti et al., 1992; Ren et al., 1993), contains a 100 amino acid region with sequence similarity to several other proteins. The presence of this putative domain in a variety of contexts in proteins implicated in signaling suggests that it might function, like SH2 and SH3 domains, to mediate protein associations. Since this region was first noted (as a duplicated region) in the platelet protein pleckstrin (Tyers et al., 1988), we propose that this putative domain be termed the pleckstrin homology, or PH, domain.