Phosphatase Family HP1

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

Subfamilies

STSs/TULAs

There are two TULAs in human, UBASH3A (STS-2 or TULA-1) and UBASH3B (STS-1 or TULA-2). Both TULAs negatively regulate the endocytosis of receptor tyrosine kinases. The UBA domain of TULA-1 and SH3-dependent Cbl-binding are required for this function. TULA-1 (STS-2) is a lymphoid protein, whereas TULA-2 (STS-1) is expressed ubiquitously. It has been shown that TULA-2 can dephosphorylate phospho-tyrosines on EGFR and Syk. The histidine phosphatase domain of TULA-2, but not of TULA-1, dephosphorylates the EGFR at multiple tyrosines, and thereby terminating its signalling and endocytosis [1]. TULA-2 decreases tyrosine phosphorylation of Syk in vivo and in vitro. Inactivated TULA-2 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 TULA-2. However, the same assay on TULA-1 shows the phosphatase activity of TULA-1 is negligible compared to TULA-2 [2]. TULA-1 is present in lobe-finned fish, birds and mammals, but not other bony fishes. TULA-2 emerged earlier than TULA-1, which is found in most metazoan, from sponge to nematodes, insects, fishes, birds, and mammals.

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 |
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 |