title: Protein kinase N (PKN) and PKN-related protein rhophilin as targets of small GTPase Rho.
abstract: The Rho guanosine 5'-triphosphatase (GTPase) cycles between the active guanosine triphosphate (GTP)-bound form and the inactive guanosine diphosphate-bound form and regulates cell adhesion and cytokinesis, but how it exerts these actions is unknown. The yeast two-hybrid system was used to clone a complementary DNA for a protein (designated Rhophilin) that specifically bound to GTP-Rho. The Rho-binding domain of this protein has 40 percent identity with a putative regulatory domain of a protein kinase, PKN. PKN itself bound to GTP-Rho and was activated by this binding both in vitro and in vivo. This study indicates that a serine-threonine protein kinase is a Rho effector and presents an amino acid sequence motif for binding to GTP-Rho that may be shared by a family of Rho target proteins.
authors.affiliation: Department of Pharmacology, Kyoto University Faculty of Medicine, Japan.
authors.forename: G
authors.initials: G
authors.lastname: Watanabe
authors.forename: Y
authors.initials: Y
authors.lastname: Saito
authors.forename: P
authors.initials: P
authors.lastname: Madaule
authors.forename: T
authors.initials: T
authors.lastname: Ishizaki
authors.forename: K
authors.initials: K
authors.lastname: Fujisawa
authors.forename: N
authors.initials: N
authors.lastname: Morii
authors.forename: H
authors.initials: H
authors.lastname: Mukai
authors.forename: Y
authors.initials: Y
authors.lastname: Ono
authors.forename: A
authors.initials: A
authors.lastname: Kakizuka
authors.forename: S
authors.initials: S
authors.lastname: Narumiya
mesh_terms: D048868:Adaptor Proteins, Signal Transducing; D000595:Amino Acid Sequence; D000818:Animals; D002460:Cell Line; D003001:Cloning, Molecular; D004789:Enzyme Activation; D020558:GTP Phosphohydrolases / Q000378:metabolism*; D019204:GTP-Binding Proteins / Q000737:chemistry / Q000378:metabolism*; D006160:Guanosine Triphosphate / Q000378:metabolism; D006801:Humans; D008565:Membrane Proteins / Q000378:metabolism*; D051379:Mice; D008969:Molecular Sequence Data; D010766:Phosphorylation; D011493:Protein Kinase C / Q000737:chemistry / Q000378:metabolism*; D017346:Protein Serine-Threonine Kinases; D011993:Recombinant Fusion Proteins / Q000378:metabolism; D012441:Saccharomyces cerevisiae / Q000235:genetics; D015398:Signal Transduction; D018631:ras Proteins; D020741:rho GTP-Binding Proteins; D020742:rhoA GTP-Binding Protein; D020743:rhoB GTP-Binding Protein; D000075024:rhoC GTP-Binding Protein
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D008565:Membrane Proteins; D011993:Recombinant Fusion Proteins; C097916:rhophilin; D006160:Guanosine Triphosphate; C061570:protein kinase N; D017346:Protein Serine-Threonine Kinases; D011493:Protein Kinase C; D020558:GTP Phosphohydrolases; D019204:GTP-Binding Proteins; C066690:RHOC protein, human; C512911:Rhoc protein, mouse; D018631:ras Proteins; D020741:rho GTP-Binding Proteins; D020742:rhoA GTP-Binding Protein; D020743:rhoB GTP-Binding Protein; D000075024:rhoC GTP-Binding Protein