Protein kinase N (PKN) and PKN-related protein rhophilin as targets of small GTPase Rho.
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.
Watanabe
G
G
Department of Pharmacology, Kyoto University Faculty of Medicine, Japan.
Saito
Y
Y
Madaule
P
P
Ishizaki
T
T
Fujisawa
K
K
Morii
N
N
Mukai
H
H
Ono
Y
Y
Kakizuka
A
A
Narumiya
S
S
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
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