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

One of the areas of greatest recent progress in immunology has been the elucidation of inhibitory receptors and their mode of signal transduction. A common feature of members of this growing family is expression of a conserved cytoplasmic sequence motif, the immunoreceptor tyrosine-based inhibitory motif, which functions to recruit and activate phosphatases that mediate the receptors' function. Family members include the protein tyrosine phosphatases SHP-1 (Src-homology-2-domain-containing protein tyrosine phosphatase 1) and SHP-2, which function to dephosphorylate key intermediaries in antigen receptor signaling pathways. Surprisingly, whereas most data to date support a role for SHP-1 in inhibitory signaling, SHP-2 exhibits distinct functions that appear to positively regulate receptor function.