Difference between revisions of "Phosphatase Subfamily STS"

Revision as of 01:28, 3 January 2015

Phosphatase Classification: Fold HP: Superfamily HP (histidine phosphatase): HP, branch1 family: Subfamily STS

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

STS-1 can dephosphorylate phospho-tyrosines on EGFR and Syk. 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 [1].

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 [2].

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 a lymphoid protein, whereas STS-1 is expressed ubiquitously.

References

1. 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 | PubMed ID:17880946 | HubMed [STS_1]
2. 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 | PubMed ID:18189269 | HubMed [STS_2]