Cytoplasmic protein tyrosine phosphatases SHP-1 and SHP-2: regulators of Bcell signal transduction

One of the areas of greatest recent progress in immunology has been the elu cidation of inhibitory receptors and their mode of signal transduction. A c ommon feature of members of this growing family is expression of a conserve d cytoplasmic sequence motif, the immunoreceptor tyrosine-based inhibitory motif, which functions to recruit and activate phosphatases that mediate th e receptors' function. Family members include the protein tyrosine phosphat ases SHP-1 (Src-homology-2-domain-containing protein tyrosine phosphatase 1 ) and SHP-2, which function to dephosphorylate key intermediaries in antige n receptor signaling pathways. Surprisingly, whereas most data to date supp ort a role for SHP-1 in inhibitory signaling, SHP-2 exhibits distinct funct ions that appear to positively regulate receptor function.