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Role of PRL-3, a Human Muscle-Specific Tyrosine Phosphatase, in Angiotensin-II Signaling

2001; Elsevier BV; Volume: 283; Issue: 5 Linguagem: Inglês

10.1006/bbrc.2001.4881

1090-2104

William F. Matter, Thomas Estridge, Chen Zhang, Rama M. Belagaje, Louis F. Stancato, S. Jeffrey Dixon, Brian N. Johnson, Laura J. Bloem, Todd Pickard, Mary Donaghue, Susan Acton, Raju Jeyaseelan, Vivek J. Kadambi, Chris J. Vlahos,

Galectins and Cancer Biology

Action of protein kinases and phosphatases contributes to myocardial hypertrophy. PRL-3, a protein tyrosine phosphatase, was identified in a cDNA library from an explanted human heart obtained from a patient with idiopathic cardiomyopathy. PRL-3 is expressed in heart and skeletal muscle, exhibiting approximately 76% identity to the ubiquitous tyrosine phosphatase PRL-1, which was reported to increase cell proliferation. PRL-3 was cloned into E. coli and purified using affinity chromatography. PRL-3 activity was determined using the substrate 6,8-difluoro-4-methylumbelliferyl phosphate, and was inhibited by vanadate and analogs. HEK293 cells expressing PRL-3 demonstrated increased growth rates versus nontransfected cells or cells transfected with the catalytically inactive C104S PRL-3 mutant. The tyrosine phosphatase inhibitor, potassium bisperoxo (bipyridine) oxovanadate V, normalizes the growth rate of PRL-3 expressing cells to that of parental HEK293 cells in a concentration-dependent manner. Using FLIPR analysis, parental HEK293 cells mobilize calcium when stimulated with angiotensin-II (AngII). However, calcium mobilization is inhibited in cells expressing wild-type PRL-3 when stimulated with AngII, while cells expressing the inactive mutant of PRL-3 mobilize calcium to the same extent as parental HEK293 cells. Western blots comparing PRL-3 transfected cells to parental HEK293 cells showed dephosphorylation of p130(cas) in response to AngII. These data suggest a role for PRL-3 in the modulation of intracellular calcium transients induced by AngII.