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Division of Basic Sciences, Department of Pediatrics, National Jewish Medical and Research Center, Denver, CO 80206, USA.
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.
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