title: Modulation by the ATP/GTP ratio of the phosphorylation level of P-glycoprotein and of various plasma membrane proteins of KB-V1 multidrug resistant cells.
abstract: The level of protein phosphorylation is known to affect the properties of various membrane proteins. We have previously shown that GTP is capable of greatly enhancing the phosphorylation by [gamma-32P]ATP of P-glycoprotein (Pgp) from KB-V1 cells (3). Investigating the possibility of a general modulation of [gamma-32P]ATP plasma membrane protein phosphorylation, we found that phosphorylation of other membrane proteins are also modulated by various combinations of [ATP + GTP]. The ATP/GTP ratio giving the highest phosphorylation level depended on the protein studied. Modulation of the [gamma-32P]ATP-mediated phosphorylation of numerous membrane proteins requires hydrolysis of both ATP and GTP. ADP and GDP also increased [gamma-32P]ATP-driven phosphorylation but to a lesser extent than GTP. This plasma membrane endogenous phosphorylation activity was neither inhibited by specific inhibitors of protein kinase C, nor by inhibitors of cAMP- or cGMP-dependent protein kinases or of casein kinase II, respectively. Mastoparan, a G-protein regulator, increased the phosphorylation of some proteins that were already enhanced by the presence of [ATP + GTP] mixtures, especially proteins migrating in gels at the same position as P-glycoprotein.
authors.affiliation: UPR 9003 CNRS, IRCAD, Hôpitaux Universitaires, BP 426, 67091, Strasbourg, France.
authors.forename: Isabelle H
authors.initials: IH
authors.lastname: Lelong-Rebel
authors.forename: Gérard
authors.initials: G
authors.lastname: Rebel
authors.forename: Carol O
authors.initials: CO
authors.lastname: Cardarelli
authors.forename: Ira
authors.initials: I
authors.lastname: Pastan
authors.forename: Michael M
authors.initials: MM
authors.lastname: Gottesman
mesh_terms: D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000378:metabolism*; D000255:Adenosine Triphosphate / Q000378:metabolism / Q000494:pharmacology*; D002462:Cell Membrane / Q000187:drug effects / Q000378:metabolism; D017868:Cyclic AMP-Dependent Protein Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism; D017869:Cyclic GMP-Dependent Protein Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism; D018432:Drug Resistance, Multiple; D019008:Drug Resistance, Neoplasm; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006160:Guanosine Triphosphate / Q000378:metabolism / Q000494:pharmacology*; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins; D007624:KB Cells; D008565:Membrane Proteins / Q000378:metabolism*; D010455:Peptides; D010761:Phosphorus Radioisotopes; D010766:Phosphorylation / Q000187:drug effects; D011493:Protein Kinase C / Q000037:antagonists & inhibitors / Q000378:metabolism; D014862:Wasp Venoms / Q000494:pharmacology
chemical_list: D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D004791:Enzyme Inhibitors; D036341:Intercellular Signaling Peptides and Proteins; D008565:Membrane Proteins; D010455:Peptides; D010761:Phosphorus Radioisotopes; D014862:Wasp Venoms; C037500:mastoparan; D006160:Guanosine Triphosphate; D000255:Adenosine Triphosphate; D017868:Cyclic AMP-Dependent Protein Kinases; D017869:Cyclic GMP-Dependent Protein Kinases; D011493:Protein Kinase C