Phosphatase Subfamily STS
Phosphatase Classification: Fold HP: Superfamily HP (histidine phosphatase): HP, branch1 family: Subfamily STS
Contents
Evolution
STS subfamily is found in most metazoan. Human has two STSs: STS-1 (TULA-2 or UBASH3B) and STS-2 (TULA-1 or UBASH3A). STS-2 is present in lobe-finned fish, birds and mammals, but not other bony fishes. STS-1 emerged earlier than STS-2, which is found in most metazoan, from sponge to nematodes, insects, fishes, birds, and mammals.
Domain
STS has three domains: UBA, SH3 and HP2 phosphatase domain.
Functions
Human STS-1 and STS-2 are involved in T Cell Receptor Signaling Pathways by regulating kinase Syk and ZAP-70, two members of Syk kinase subfamily.
STS-1 decreases tyrosine phosphorylation of Syk in vivo and in vitro. Inactivated STS-1 increases tyrosine phosphorylation of Syk in cells co-transfected to overexpress these proteins, thus acting as a dominant-negative form that suppresses dephosphorylation of Syk caused by endogenous STS-1. However, the same assay on STS-2 shows the phosphatase activity of STS-2 is negligible compared to STS-1 [1]. In addition, both STS-1 and STS-2 regulates kinase ZAP-70 activation [2].
Human STS-1 can also dephosphorylate phospho-tyrosines on EGFR. The histidine phosphatase domain of STS-1, but not of STS-2, dephosphorylates the EGFR at multiple tyrosines, and thereby terminating its signalling and endocytosis [3].
Both human STSs negatively regulate the endocytosis of receptor tyrosine kinases. The UBA domain of STS-2 and SH3-dependent Cbl-binding are required for this function. STS-2 is predominantly in naive and mature T cells , whereas STS-1 is expressed ubiquitously.
References
- Agrawal R, Carpino N, and Tsygankov A. TULA proteins regulate activity of the protein tyrosine kinase Syk. J Cell Biochem. 2008 Jun 1;104(3):953-64. DOI:10.1002/jcb.21678 |
- Raguz J, Wagner S, Dikic I, and Hoeller D. Suppressor of T-cell receptor signalling 1 and 2 differentially regulate endocytosis and signalling of receptor tyrosine kinases. FEBS Lett. 2007 Oct 2;581(24):4767-72. DOI:10.1016/j.febslet.2007.08.077 |
- Carpino N, Turner S, Mekala D, Takahashi Y, Zang H, Geiger TL, Doherty P, and Ihle JN. Regulation of ZAP-70 activation and TCR signaling by two related proteins, Sts-1 and Sts-2. Immunity. 2004 Jan;20(1):37-46. DOI:10.1016/s1074-7613(03)00351-0 |
