Regulation of GRP1-catalyzed ADP ribosylation factor guanine nucleotide exchange by phosphatidylinositol 3,4,5-trisphosphate
Authors
Klarlund, Jes K.Rameh, Lucia E.
Cantley, Lewis C.
Buxton, Joanne M.
Holik, John
Sakelis, Christoper
Patki, Varsha
Corvera, Silvia
Czech, Michael P.
UMass Chan Affiliations
Department of Biochemistry and Molecular PharmacologyProgram in Molecular Medicine
Document Type
Journal ArticlePublication Date
1998-01-27Keywords
1-Phosphatidylinositol 3-KinaseADP-Ribosylation Factor 1
ADP-Ribosylation Factors
Animals
Binding Sites
Carrier Proteins
Catalysis
Cells, Cultured
GTP-Binding Proteins
Guanosine 5'-O-(3-Thiotriphosphate)
Inositol Phosphates
Phosphatidylinositol Phosphates
Receptors, Cytoplasmic and Nuclear
Recombinant Proteins
Spodoptera
Amino Acids, Peptides, and Proteins
Biochemistry
Cells
Enzymes and Coenzymes
Heterocyclic Compounds
Lipids
Nucleic Acids, Nucleotides, and Nucleosides
Metadata
Show full item recordAbstract
Cellular levels of phosphatidylinositol 3,4,5-trisphosphate (PtdIns(3,4,5)P3) are rapidly elevated in response to activation of growth factor receptor tyrosine kinases. This polyphosphoinositide binds the pleckstrin homology (PH) domain of GRP1, a protein that also contains 200 residues with high sequence similarity to a segment of the yeast Sec7 protein that functions as an ADP ribosylation exchange factor (ARF) (Klarlund, J., Guilherme, A., Holik, J. J., Virbasius, J. V., Chawla, A., and Czech, M. P. (1997) Science 275, 1927-1930). Here we show that dioctanoyl PtdIns(3,4,5)P3 binds the PH domain of GRP1 with a Kd = 0.5 microM, an affinity 2 orders of magnitude greater than dioctanoyl-PtdIns(4,5)P2. Further, the Sec7 domain of GRP1 is found to catalyze guanine nucleotide exchange of ARF1 and -5 but not ARF6. Importantly, PtdIns(3,4,5)P3, but not PtdIns(4,5)P2, markedly enhances the ARF exchange activity of GRP1 in a reaction mixture containing dimyristoylphosphatidylcholine micelles, 3-[(3-cholamidopropyl)dimethylammonio]-1-propanesulfonic acid, and a low concentration of sodium cholate. PtdIns(3,4,5)P3-mediated ARF nucleotide exchange through GRP1 is selectively blocked by 100 microM inositol 1,3,4,5-tetrakisphosphate, which also binds the PH domain of GRP1. Taken together, these data are consistent with the hypothesis that selective recruitment of GRP1 to PtdIns(3,4,5)P3 in membranes activates ARF1 and -5, known regulators of intracellular membrane trafficking.Source
J Biol Chem. 1998 Jan 23;273(4):1859-62.
DOI
10.1074/jbc.273.4.1859Permanent Link to this Item
http://hdl.handle.net/20.500.14038/42434PubMed ID
9442017Related Resources
ae974a485f413a2113503eed53cd6c53
10.1074/jbc.273.4.1859