1. Protein tyrosine phosphatases (Shp-1, Shp-2) with SH2 domains. Are recruited to ITIM motifs of receptor tyrosine kinases and play an important role in the control of cytokine signalling. Shp-1 (haematopoietic cell phosphatase, PTP1C, PTPN6, 595 aa) is important in regulating antigen responses in T-cells and the mouse mutant (motheaten) is immunosuppressed. Shp-2 (Syp, PTP2C, PTPN11, 593 aa) is more ubiquitously expressed and functions downstream of a variety of growth factor receptors and has a role in cell spreading and migration; the homozygous mouse knockout is embryonic lethal. An important substrate for both phosphatases is shps1 (shp-substrate 1, signal regulatory protein α1, SIRP-α1, 503 aa) when it has been phosphorylated by receptor tyrosine kinases.
2. Small heterodimer partner (shp, 257 aa), an orphan nuclear receptor belonging to the nuclear receptor superfamily of transcription factors. Interacts with various other receptors such as the retinoid receptor and seems to be a negative regulator of signalling pathways. Mutations in the gene are associated with early-onset mild obesity.
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