Suppressor of T cell signaling 1 phosphatase (Sts-1)

Suppressor of T cell signaling 1 phosphatase (Sts-1, also known as UBASH3B or TULA-2) is a member of the histidine phosphatase superfamily that functions as a negative regulator of signaling pathways downstream of tyrosine kinase receptors, most notably the TCR and BCR in immune cells[1][3][7]. Sts-1 contains a C-terminal phosphoglycerate mutase (PGM)–like domain responsible for its intrinsic tyrosine phosphatase activity, as well as ubiquitin (UBA) and SH3 domains[7]. It dephosphorylates proteins such as Zap-70, SYK, EGFR, PDGFR, and Bcr-Abl, modulating immune and cell growth pathways[1][7]. Its inactivation has been linked to increased resistance to certain infections, such as systemic candidiasis, making it a potential therapeutic target for immune modulation and anti-infective strategies[5][8]. Selective small-molecule inhibitors have been identified, including PHPS1 and experimental tetracycline and azo dye derivatives, supporting druggability and experimental modulation of Sts-1 function[2][4][5].

Other names

UBASH3BTULA-2TULA2suppressor of T-cell receptor signaling-1suppressor of T-cell signaling 1

Competitive inhibition of the phosphatase active site; Negative regulation of key tyrosine kinases (e.g., dephosphorylation of Zap-70, SYK, EGFR, PDGFR, Bcr-Abl)