title: An intracellular guanine nucleotide release protein for G0. GAP-43 stimulates isolated alpha subunits by a novel mechanism.
abstract: G protein-coupled membrane receptors activate G proteins by enhancing guanine nucleotide exchange. G0 is a major component of the growing regions (growth cones) of neurons. GAP-43 is a neuronal protein associated with the cytosolic face of the growth cone plasma membrane and stimulates binding of guanosine 5'-3-O-(thio)triphosphate (GTP gamma S) to Go (Strittmatter, S. M., Valenzuela, D., Kennedy, T. E., Neer, E. J., and Fishman, M. C. (1990) Nature 344, 836-841). Here we have examined the mechanism by which GAP-43 affects G0. Like G protein-coupled receptors, GAP-43 enhances GDP release from G0, increases the initial rate of GTP gamma S binding, and increases the GTPase activity of Go, all without altering the intrinsic kappa cat for the GTPase. Unlike the case for receptors, however, the GAP-43 effect is not blocked by pertussis toxin, nor affected by the presence or absence of beta gamma or of phospholipids. There is specificity to the interaction, in that GAP-43 increases GTP gamma S binding to recombinant alpha o and alpha i1, but not to recombinant alpha s. Thus, GAP-43 is a guanine nucleotide release protein with a novel mechanism of action, potentially controlling membrane-associated G proteins from within the cell.
authors.affiliation: Development Biology Laboratory, Massachusetts General Hospital-East, Charlestown 02129.
authors.forename: S M
authors.initials: SM
authors.lastname: Strittmatter
authors.forename: D
authors.initials: D
authors.lastname: Valenzuela
authors.forename: Y
authors.initials: Y
authors.lastname: Sudo
authors.forename: M E
authors.initials: ME
authors.lastname: Linder
authors.forename: M C
authors.initials: MC
authors.lastname: Fishman
mesh_terms: D000818:Animals; D001921:Brain / Q000378:metabolism; D002417:Cattle; D019922:GAP-43 Protein; D019204:GTP-Binding Proteins / Q000378:metabolism*; D006150:Guanine Nucleotides / Q000378:metabolism*; D016244:Guanosine 5'-O-(3-Thiotriphosphate) / Q000378:metabolism; D006153:Guanosine Diphosphate / Q000378:metabolism; D006160:Guanosine Triphosphate / Q000378:metabolism; D007700:Kinetics; D008081:Liposomes; D046911:Macromolecular Substances; D008562:Membrane Glycoproteins / Q000302:isolation & purification / Q000378:metabolism*; D009243:NAD / Q000378:metabolism; D009419:Nerve Tissue Proteins / Q000302:isolation & purification / Q000378:metabolism*; D037342:Pertussis Toxin; D010713:Phosphatidylcholines; D010750:Phosphoproteins / Q000378:metabolism; D011485:Protein Binding; D051381:Rats; D011994:Recombinant Proteins / Q000378:metabolism; D010566:Virulence Factors, Bordetella / Q000494:pharmacology
chemical_list: D019922:GAP-43 Protein; D006150:Guanine Nucleotides; D008081:Liposomes; D046911:Macromolecular Substances; D008562:Membrane Glycoproteins; D009419:Nerve Tissue Proteins; D010713:Phosphatidylcholines; D010750:Phosphoproteins; D011994:Recombinant Proteins; D010566:Virulence Factors, Bordetella; D009243:NAD; D006153:Guanosine Diphosphate; D016244:Guanosine 5'-O-(3-Thiotriphosphate); D006160:Guanosine Triphosphate; D037342:Pertussis Toxin; D019204:GTP-Binding Proteins