PMID- 7520867 OWN - NLM STAT- MEDLINE DCOM- 19940929 LR - 20220511 IS - 0261-4189 (Print) IS - 1460-2075 (Electronic) IS - 0261-4189 (Linking) VI - 13 IP - 16 DP - 1994 Aug 15 TI - PTP-PEST: a protein tyrosine phosphatase regulated by serine phosphorylation. PG - 3763-71 AB - The protein tyrosine phosphatase PTP-PEST is an 88 kDa cytosolic enzyme which is ubiquitously expressed in mammalian tissues. We have expressed PTP-PEST using recombinant baculovirus, and purified the protein essentially to homogeneity in order to investigate phosphorylation as a potential mechanism of regulation of the enzyme. PTP-PEST is phosphorylated in vitro by both cyclic AMP-dependent protein kinase (PKA) and protein kinase C (PKC) at two major sites, which we have identified as Ser39 and Ser435. PTP-PEST is also phosphorylated on both Ser39 and Ser435 following treatment of intact HeLa cells with TPA, forskolin or isobutyl methyl xanthine (IBMX). Phosphorylation of Ser39 in vitro decreases the activity of PTP-PEST by reducing its affinity for substrate. In addition, PTP-PEST immunoprecipitated from TPA-treated cells displayed significantly lower PTP activity than enzyme obtained from untreated cells. Our results suggest that both PKC and PKA are capable of phosphorylating, and therefore inhibiting, PTP-PEST in vivo, offering a mechanism whereby signal transduction pathways acting through either PKA or PKC may directly influence cellular processes involving reversible tyrosine phosphorylation. FAU - Garton, A J AU - Garton AJ AD - Cold Spring Harbor Laboratory, NY 11724-2208. FAU - Tonks, N K AU - Tonks NK LA - eng GR - CA53840/CA/NCI NIH HHS/United States PT - Journal Article PT - Research Support, Non-U.S. Gov't PT - Research Support, U.S. Gov't, P.H.S. PL - England TA - EMBO J JT - The EMBO journal JID - 8208664 RN - 0 (Phorbol Esters) RN - 0 (Phosphopeptides) RN - 0 (Recombinant Proteins) RN - 1F7A44V6OU (Colforsin) RN - 452VLY9402 (Serine) RN - EC 2.7.11.11 (Cyclic AMP-Dependent Protein Kinases) RN - EC 2.7.11.13 (Protein Kinase C) RN - EC 3.1.3.48 (PTPN12 protein, human) RN - EC 3.1.3.48 (Protein Tyrosine Phosphatase, Non-Receptor Type 12) RN - EC 3.1.3.48 (Protein Tyrosine Phosphatases) RN - NI40JAQ945 (Tetradecanoylphorbol Acetate) RN - TBT296U68M (1-Methyl-3-isobutylxanthine) SB - IM MH - 1-Methyl-3-isobutylxanthine/pharmacology MH - Baculoviridae/genetics MH - Colforsin/pharmacology MH - Cyclic AMP-Dependent Protein Kinases/metabolism MH - *Gene Expression Regulation, Enzymologic MH - HeLa Cells/enzymology/metabolism MH - Humans MH - Peptide Mapping MH - Phorbol Esters MH - Phosphopeptides/analysis MH - Phosphorylation/drug effects MH - Protein Kinase C/metabolism MH - Protein Tyrosine Phosphatase, Non-Receptor Type 12 MH - Protein Tyrosine Phosphatases/genetics/*metabolism MH - Recombinant Proteins/metabolism MH - Sequence Analysis MH - Serine/metabolism MH - Tetradecanoylphorbol Acetate/pharmacology PMC - PMC395289 EDAT- 1994/08/15 00:00 MHDA- 1994/08/15 00:01 PMCR- 1995/08/15 CRDT- 1994/08/15 00:00 PHST- 1994/08/15 00:00 [pubmed] PHST- 1994/08/15 00:01 [medline] PHST- 1994/08/15 00:00 [entrez] PHST- 1995/08/15 00:00 [pmc-release] AID - 10.1002/j.1460-2075.1994.tb06687.x [doi] PST - ppublish SO - EMBO J. 1994 Aug 15;13(16):3763-71. doi: 10.1002/j.1460-2075.1994.tb06687.x.