title: Alpha 4 associates with protein phosphatases 2A, 4, and 6.
abstract: Protein phosphatases participate in the regulation of a variety of cellular processes. Control of their enzymatic activity and specificity is made possible largely by an array of regulatory subunits. Novel serine/threonine phosphatases--PP4 and PP6 in human cells--have been discovered recently, for which regulatory subunits are yet to be identified. We report here the identification of a potential regulatory subunit of these phosphatases. Using the yeast two-hybrid system, we have found that alpha 4, a previously identified phosphoprotein, associates constitutively with the catalytic subunits of PP4, PP6, and both isoforms of PP2A. These interactions have been confirmed by direct binding and do not require phosphorylation of alpha 4, although it is unclear whether alpha 4 phosphorylation has any effect on its association with the phosphatases. The binding activity appears to reside in the N-terminal 50 amino acids of the phosphatases, consistent with a previous observation that the first 55 residues of PPV, a Drosophila homolog of PP6, may harbor the element for regulation. alpha 4 shares 37% sequence homology with Tap42, an S. cerevisiae protein that has been reported to associate with PP2A and Sit4 (yeast homolog of PP6) and comprises a regulatory component in the rapamycin-sensitive Tor signalling pathway. By analogy, alpha 4 and its associated phosphatases may participate in the mammalian rapamycin-sensitive pathway mediated by FRAP.
authors.affiliation: Howard Hughes Medical Institute, Department of Chemistry & Chemical Biology, Harvard University, Cambridge, Massachusetts 02138, USA.
authors.forename: J
authors.initials: J
authors.lastname: Chen
authors.forename: R T
authors.initials: RT
authors.lastname: Peterson
authors.forename: S L
authors.initials: SL
authors.lastname: Schreiber
mesh_terms: D048868:Adaptor Proteins, Signal Transducing; D002453:Cell Cycle / Q000502:physiology; D003001:Cloning, Molecular; D004926:Escherichia coli / Q000235:genetics; D015870:Gene Expression / Q000235:genetics; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins; D007527:Isoenzymes / Q000737:chemistry; D019169:Jurkat Cells; D018832:Molecular Chaperones; D009842:Oligopeptides; D010455:Peptides / Q000235:genetics; D010749:Phosphoprotein Phosphatases / Q000378:metabolism*; D010750:Phosphoproteins / Q000378:metabolism*; D011090:Polyenes / Q000494:pharmacology; D011485:Protein Binding / Q000502:physiology; D011994:Recombinant Proteins / Q000235:genetics; D015398:Signal Transduction / Q000502:physiology; D020123:Sirolimus; D014162:Transfection / Q000235:genetics
chemical_list: D048868:Adaptor Proteins, Signal Transducing; C490467:IGBP1 protein, human; D047908:Intracellular Signaling Peptides and Proteins; D007527:Isoenzymes; D018832:Molecular Chaperones; D009842:Oligopeptides; D010455:Peptides; D010750:Phosphoproteins; D011090:Polyenes; D011994:Recombinant Proteins; C085706:FLAG peptide; D010749:Phosphoprotein Phosphatases; D020123:Sirolimus