Similarities in Function and Gene Structure of Cytohesin-4 and Cytohesin-1, Guanine Nucleotide-exchange Proteins for ADP-ribosylation Factors
| Autor: | Victor J. Ferrans, Joel Moss, Kazuyo Takeda, Sei-Chang Kim, Akira Togawa, Martha Kirby, Martha Vaughan, Ronald Adamik, Masahito Ogasawara |
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| Rok vydání: | 2000 |
| Předmět: |
DNA
Complementary ADP ribosylation factor Sequence analysis Molecular Sequence Data Guanosine Sequence alignment GTPase Biology Biochemistry Cell Line chemistry.chemical_compound Animals Guanine Nucleotide Exchange Factors Humans Amino Acid Sequence Cloning Molecular Molecular Biology Peptide sequence ADP-Ribosylation Factors cDNA library Cell Biology Molecular biology Recombinant Proteins Pleckstrin homology domain chemistry Cell Adhesion Molecules Sequence Alignment Sequence Analysis |
| Zdroj: | Journal of Biological Chemistry. 275:3221-3230 |
| ISSN: | 0021-9258 |
| Popis: | Activation of ADP-ribosylation factors (ARFs), approximately 20-kDa GTPases that are inactive in the GDP-bound form, depends on guanine nucleotide-exchange proteins (GEPs) to accelerate GTP binding. A novel ARF GEP, designated cytohesin-4, was cloned from a human brain cDNA library. Deduced amino acid sequence of the 47-kDa protein contains the same structural components present in cytohesin -1, -2, and -3, including an approximately 200-amino acid Sec7 domain with an approximately 100-residue pleckstrin homology domain near the C terminus. The Sec7 domain sequence is 77% identical to those of other cytohesins. Structures of the cytohesin-4 and cytohesin-1 genes were remarkably similar, except for an extra 3-base pair (GAG) exon present in cytohesin-1. Two mRNAs with and without the 3-base pair sequence were found in brain in different ratios for cytohesin-1, -2, and -3 but not cytohesin-4. Recombinant cytohesin-4 stimulated guanosine 5'-3-O-(thio)triphosphate binding by human ARF1 and ARF5 but not ARF6. Like other cytohesins and unlike the approximately 200-kDa ARF GEPs, it was not inhibited by brefeldin A. A cytohesin-4 mRNA of approximately 3.7 kilobases, abundant in leukocytes, was not detected in most tissues. Among separated populations of blood cells, approximately 90% of CD33(+) (monocytes), 80% of CD2(+) (NK/T), and 10-20% of CD19(+) (B) cells contained cytohesin-4 mRNA by in situ hybridization. Thus, in gene structure and brefeldin A-insensitive GEP activity, cytohesin-4 resembles other cytohesins, but its tissue distribution differs considerably, consistent with a different specific function. |
| Databáze: | OpenAIRE |
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