The yeast phosphotyrosyl phosphatase activator is part of the Tap42-phosphatase complexes.
Phosphotyrosyl phosphatase activator PTPA is a type 2A phosphatase regulatory protein that possesses an ability to stimulate the phosphotyrosyl phosphatase activity of PP2A in vitro. In yeast Saccharomyces cerevisiae, PTPA is encoded by two related genes, RRD1 and RRD2, whose products are 38 and 37% identical, respectively, to the mammalian PTPA. Inactivation of either gene renders yeast cells rapamycin resistant. In this study, we investigate the mechanism underling rapamycin resistance associated with inactivation of PTPA in yeast. We show that the yeast PTPA is an integral part of the Tap42-phosphatase complexes that act downstream of the Tor proteins, the target of rapamycin. We demonstrate a specific interaction of Rrd1 with the Tap42-Sit4 complex and that of Rrd2 with the Tap42-PP2Ac complex. A small portion of PTPA also is found to be associated with the AC dimeric core of PP2A, but the amount is significantly less than that associated with the Tap42-containing complexes. In addition, our results show that the association of PTPA with Tap42-phosphatase complexes is rapamycin sensitive, and importantly, that rapamycin treatment results in release of the PTPA-phosphatase dimer as a functional phosphatase unit.
Zheng
Yin
Y
Department of Pharmacology, University of Pittsburgh School of Medicine, PA 15213, USA.
Jiang
Yu
Y
D048868:Adaptor Proteins, Signal Transducing; D004789:Enzyme Activation / Q000187:drug effects; D047908:Intracellular Signaling Peptides and Proteins; D046912:Multiprotein Complexes / Q000737:chemistry / Q000378:metabolism; D009154:Mutation / Q000235:genetics; D019696:Peptidylprolyl Isomerase; D010749:Phosphoprotein Phosphatases / Q000235:genetics / Q000378:metabolism; D011485:Protein Binding / Q000187:drug effects; D054648:Protein Phosphatase 2; D012441:Saccharomyces cerevisiae / Q000201:enzymology* / Q000235:genetics; D029701:Saccharomyces cerevisiae Proteins / Q000235:genetics / Q000378:metabolism*; D020123:Sirolimus / Q000494:pharmacology
D048868:Adaptor Proteins, Signal Transducing; D047908:Intracellular Signaling Peptides and Proteins; D046912:Multiprotein Complexes; C502933:RRD2 protein, S cerevisiae; D029701:Saccharomyces cerevisiae Proteins; C100984:TAP42 protein, S cerevisiae; D010749:Phosphoprotein Phosphatases; D054648:Protein Phosphatase 2; C104343:SIT4 protein, S cerevisiae; D019696:Peptidylprolyl Isomerase; C490203:RRD1 protein, S cerevisiae; D020123:Sirolimus