SHP-1
SHP-1 (PTPN6) is a hematopoietic-restricted non-receptor phosphatase built from two N-terminal SH2 domains, a catalytic domain, and a regulatory C-terminal tail. It is recruited to ITIM motifs of inhibitory receptors such as KIRs, LILRs, PIR-B, CD22, and PD-1, and it downregulates antigen receptor and cytokine receptor signaling by dephosphorylating proximal kinases. Loss of SHP-1 causes the motheaten phenotype in mice, characterized by lethal autoimmunity and myeloid expansion, underscoring its checkpoint role in immunity. SHP-1 is often silenced by promoter methylation in lymphomas and nasopharyngeal carcinoma, acting as a tumor suppressor, and recombinant SHP-1 supports ITIM signaling and phosphatase-inhibitor studies.
