GAP domains responsible for ras p21-dependent inhibition of muscarinic atrial K+ channel currents.
The interaction between the low molecular weight G protein ras p21 and a guanosine triphosphatase activating protein (GAP) uncouples a heterotrimeric G protein (Gk) from muscarinic receptors. Through the use of isolated atrial cell membranes and genetically engineered GAP deletion mutants, the src homology regions (SH2-SH3) at the amino terminus of GAP have been identified as the domains responsible for this effect. Deletion of the domain required to stimulate the guanosine triphosphatase activity of ras p21 relieves the requirement for ras p21 in this system. A model is presented that suggests that ras p21 induces a conformational change in GAP, which allows the SH2-SH3 regions of GAP to function.
Martin
G A
GA
Department of Molecular Biology, Cetus Corporation, Emeryville, CA 94608.
Yatani
A
A
Clark
R
R
Conroy
L
L
Polakis
P
P
Brown
A M
AM
McCormick
F
F
D000818:Animals; D016367:Baculoviridae; D002462:Cell Membrane / Q000378:metabolism; D002478:Cells, Cultured; D003001:Cloning, Molecular; D019204:GTP-Binding Proteins / Q000502:physiology*; D020690:GTPase-Activating Proteins; D005818:Genetic Engineering; D005822:Genetic Vectors; D016244:Guanosine 5'-O-(3-Thiotriphosphate) / Q000494:pharmacology; D006160:Guanosine Triphosphate / Q000494:pharmacology; D006168:Guinea Pigs; D006321:Heart / Q000502:physiology*; D006325:Heart Atria; D008954:Models, Biological; D016133:Polymerase Chain Reaction; D015221:Potassium Channels / Q000187:drug effects / Q000502:physiology*; D011506:Proteins / Q000235:genetics / Q000502:physiology*; D016283:Proto-Oncogene Proteins p21(ras) / Q000378:metabolism*; D011976:Receptors, Muscarinic / Q000187:drug effects / Q000502:physiology*; D020703:ras GTPase-Activating Proteins
D020690:GTPase-Activating Proteins; D015221:Potassium Channels; D011506:Proteins; D011976:Receptors, Muscarinic; D020703:ras GTPase-Activating Proteins; D016244:Guanosine 5'-O-(3-Thiotriphosphate); D006160:Guanosine Triphosphate; D019204:GTP-Binding Proteins; D016283:Proto-Oncogene Proteins p21(ras)