RGSZ1, a Gz-selective regulator of G protein signaling whose action is sensitive to the phosphorylation state of Gzalpha.
Regulators of G protein signaling (RGS) are a family of proteins that attenuate the activity of the trimeric G proteins. RGS proteins act as GTPase-activating proteins (GAPs) for the alpha subunits of several trimeric G proteins, much like the GAPs that regulate the activity of monomeric G proteins such as Ras. RGS proteins have been cloned from many eukaryotes, and those whose biochemical activity has been characterized regulate the members of the Gi family of G proteins; some forms can also act on Gq proteins. In an ongoing effort to elucidate the role of Gzalpha in cell signaling, the yeast two-hybrid system was employed to identify proteins that could interact with a mutationally activated form of Gzalpha. A novel RGS, termed RGSZ1, was identified that is most closely related to two existing RGS proteins termed RetRGS1 and GAIP. Northern blot analysis revealed that expression of RGSZ1 was limited to brain, and expression was particularly high in the caudate nucleus. Biochemical characterization of recombinant RGSZ1 protein revealed that RGSZ1 was indeed a GAP and, most significantly, showed a marked preference for Gzalpha over other members of the Gialpha family. Phosphorylation of Gzalpha by protein kinase C, an event known to occur in cells and that was previously shown to influence alpha-betagamma interactions of Gz, rendered the G protein much less susceptible to RGSZ1 action.
Glick
J L
JL
Department of Biochemistry, Duke University Medical Center, Durham, North Carolina 27710-3686, USA.
Meigs
T E
TE
Miron
A
A
Casey
P J
PJ
D000595:Amino Acid Sequence; D001921:Brain / Q000378:metabolism; D003001:Cloning, Molecular; D044385:GTP-Binding Protein alpha Subunits; D019204:GTP-Binding Proteins / Q000737:chemistry* / Q000502:physiology*; D020690:GTPase-Activating Proteins; D015870:Gene Expression / Q000235:genetics; D006160:Guanosine Triphosphate / Q000378:metabolism; D020962:Heterotrimeric GTP-Binding Proteins; D006801:Humans; D007700:Kinetics; D008565:Membrane Proteins / Q000737:chemistry*; D008969:Molecular Sequence Data; D009419:Nerve Tissue Proteins / Q000737:chemistry*; D010766:Phosphorylation; D011493:Protein Kinase C / Q000378:metabolism; D011499:Protein Processing, Post-Translational / Q000502:physiology; D011506:Proteins / Q000737:chemistry*; D020710:RGS Proteins; D012333:RNA, Messenger / Q000378:metabolism; D011994:Recombinant Proteins / Q000737:chemistry; D017422:Sequence Analysis, DNA; D017386:Sequence Homology, Amino Acid; D015398:Signal Transduction / Q000502:physiology*; D020703:ras GTPase-Activating Proteins
C099387:GNAZ protein, human; D044385:GTP-Binding Protein alpha Subunits; D020690:GTPase-Activating Proteins; D008565:Membrane Proteins; D009419:Nerve Tissue Proteins; D011506:Proteins; D020710:RGS Proteins; C115120:RGS20 protein, human; D012333:RNA, Messenger; D011994:Recombinant Proteins; D020703:ras GTPase-Activating Proteins; D006160:Guanosine Triphosphate; D011493:Protein Kinase C; D019204:GTP-Binding Proteins; D020962:Heterotrimeric GTP-Binding Proteins