PMID- 10535749 OWN - NLM STAT- MEDLINE DCOM- 19991104 LR - 20190623 IS - 0006-2952 (Print) IS - 0006-2952 (Linking) VI - 58 IP - 10 DP - 1999 Nov 15 TI - Differential phosphorylation of sites in the linker region of P-glycoprotein by protein kinase C isozymes alpha, betaI, betaII, gamma, delta, epsilon, eta, and zeta. PG - 1587-92 AB - To determine whether individual protein kinase C (PKC) isozymes differentially phosphorylate sites in the linker region of human P-glycoprotein (P-gp), we used a synthetic peptide substrate, PG-2, exactly corresponding to amino acid residues spanning the region 656-689 of the multidrug resistance gene (MDRI). All tested PKC isozymes phosphorylated PG-2. The maximum phosphate incorporation by calcium-dependent PKC isozymes alpha, betaI, betaII, and gamma was 3, 2, 2, and 3 mol phosphate/mol PG-2, respectively. The maximum phosphate incorporation by calcium-independent isozymes delta, epsilon, eta, and zeta was 1.5, 0.5, 1.5, and 1.5 mol phosphate/mol PG-2, respectively. Two-dimensional tryptic phosphopeptide mapping indicated differential phosphorylation of the PKC consensus sites Ser-661, Ser-667, and Ser-671 by individual isozymes, which may be functionally significant. These data suggest that differential phosphorylation by PKC isoenzymes of PKC sites within the P-gp linker region may play a role in modulating P-gp activity. FAU - Sachs, C W AU - Sachs CW AD - Department of Medicine, Duke University, Durham, NC, USA. FAU - Chambers, T C AU - Chambers TC FAU - Fine, R L AU - Fine RL LA - eng GR - 5R21 CA 66228-02/CA/NCI NIH HHS/United States PT - Journal Article PT - Research Support, Non-U.S. Gov't PT - Research Support, U.S. Gov't, Non-P.H.S. PT - Research Support, U.S. Gov't, P.H.S. PL - England TA - Biochem Pharmacol JT - Biochemical pharmacology JID - 0101032 RN - 0 (ATP Binding Cassette Transporter, Subfamily B, Member 1) RN - 0 (Isoenzymes) RN - 0 (Peptide Fragments) RN - 0 (Phosphopeptides) RN - 0 (Recombinant Proteins) RN - EC 2.7.11.13 (Protein Kinase C) SB - IM MH - ATP Binding Cassette Transporter, Subfamily B, Member 1/*metabolism MH - Amino Acid Sequence MH - Humans MH - In Vitro Techniques MH - Isoenzymes/*metabolism MH - Molecular Sequence Data MH - Peptide Fragments/metabolism MH - Peptide Mapping MH - Phosphopeptides/analysis MH - Phosphorylation MH - Protein Kinase C/*metabolism MH - Recombinant Proteins/metabolism EDAT- 1999/10/27 00:00 MHDA- 1999/10/27 00:01 CRDT- 1999/10/27 00:00 PHST- 1999/10/27 00:00 [pubmed] PHST- 1999/10/27 00:01 [medline] PHST- 1999/10/27 00:00 [entrez] AID - S0006295299002403 [pii] AID - 10.1016/s0006-2952(99)00240-3 [doi] PST - ppublish SO - Biochem Pharmacol. 1999 Nov 15;58(10):1587-92. doi: 10.1016/s0006-2952(99)00240-3.