Selective activation of effector pathways by brain-specific G protein beta5.
While multiple G protein beta and gamma subunit isoforms have been identified, the implications of this potential diversity of betagamma heterodimers for signaling through betagamma-regulated effector pathways remains unclear. Furthermore the molecular mechanism(s) by which the betagamma complex modulates diverse mammalian effector molecules is unknown. Effector signaling by the structurally distinct brain-specific beta5 subunit was assessed by transient cotransfection with gamma2 in COS cells and compared with beta1. Transfection of either beta1 or beta5 with gamma2 stimulated the activity of cotransfected phospholipase C-beta2 (PLC-beta2), as previously reported. In contrast, cotransfection of beta1 but not beta5 with gamma2 stimulated the mitogen-activated protein kinase (MAPK) and c-Jun N-terminal kinase (JNK) pathways even though the expression of beta5 in COS cells was evident by immunoblotting. The G protein beta5 expressed in transfected COS cells was properly folded as its pattern of stable C-terminal proteolytic fragments was identical to that of native brain beta5. The inability of beta5 to activate the MAPK and JNK pathways was not overcome by cotransfection with three additional Ggamma isoforms. These results suggest it is the Gbeta subunit which determines the pattern of downstream signaling by the betagamma complex and imply that the structural features of the betagamma complex mediating effector regulation may differ among effectors.
Zhang
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Metabolic Diseases Branch, NIDDK, National Institutes of Health, Bethesda, Maryland 20892, USA. wfs@helix.nih.gov
Coso
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Lee
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Gutkind
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Simonds
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D000818:Animals; D001921:Brain / Q000378:metabolism*; D019556:COS Cells; D017871:Calcium-Calmodulin-Dependent Protein Kinases / Q000378:metabolism; D004789:Enzyme Activation; D044387:GTP-Binding Protein beta Subunits; D019204:GTP-Binding Proteins / Q000378:metabolism*; D020962:Heterotrimeric GTP-Binding Proteins; D007527:Isoenzymes / Q000378:metabolism; D048031:JNK Mitogen-Activated Protein Kinases; D051379:Mice; D048052:Mitogen-Activated Protein Kinase 3; D020928:Mitogen-Activated Protein Kinases; D008970:Molecular Weight; D054799:Phospholipase C beta; D011994:Recombinant Proteins / Q000378:metabolism; D014162:Transfection; D010738:Type C Phospholipases / Q000378:metabolism
D044387:GTP-Binding Protein beta Subunits; C094668:Gnb5 protein, mouse; D007527:Isoenzymes; D011994:Recombinant Proteins; D017871:Calcium-Calmodulin-Dependent Protein Kinases; D048031:JNK Mitogen-Activated Protein Kinases; D048052:Mitogen-Activated Protein Kinase 3; D020928:Mitogen-Activated Protein Kinases; D010738:Type C Phospholipases; D054799:Phospholipase C beta; C518034:Plcb1 protein, mouse; C518037:Plcb2 protein, mouse; D019204:GTP-Binding Proteins; D020962:Heterotrimeric GTP-Binding Proteins