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GAP‐43 Augmentation of G Protein‐Mediated Signal Transduction Is Regulated by Both Phosphorylation and Palmitoylation
Author(s) -
Nakamura Fumio,
Strittmatter Philipp,
Strittmatter Stephen M.
Publication year - 1998
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1046/j.1471-4159.1998.70030983.x
Subject(s) - palmitoylation , calmodulin , gap 43 protein , protein kinase a , signal transduction , phosphorylation , microbiology and biotechnology , biology , protein kinase c , xenopus , gtpase activating protein , g protein , cgmp dependent protein kinase , biochemistry , mitogen activated protein kinase kinase , enzyme , immunohistochemistry , cysteine , gene , immunology
The neuronal protein GAP‐43 is concentrated at the growth cone membrane, where it is thought to amplify the signal transduction process. As a model for its neuronal effects, GAP‐43 protein injection into Xenopus laevis oocytes strongly augments the calcium‐sensitive chloride current evoked by the G protein‐coupled receptor stimulation. We have now examined a series of GAP‐43 mutants in this system and determined those regions of GAP‐43 required for this increase in current flux. As expected, palmitoylation inhibits signal amplification in oocytes by blocking G protein activation. Unexpectedly, a second domain of GAP‐43 (residues 35–50) containing a protein kinase C phosphorylation site at residue 41 is also necessary for augmentation of G protein‐coupled signals in oocytes. This region is not required for activation of isolated G o but is necessary for GAP‐43 binding to isolated calmodulin and to isolated protein kinase C. Substitution of Asp for Ser 41 inactivates GAP‐43 as a signal facilitator in oocytes. This mutation blocks GAP‐43 binding to both protein kinase C and calmodulin. Thus, GAP‐43 regulates an oocyte signaling cascade via coordinated, simultaneous G protein activation and interaction with either calmodulin or protein kinase C.