Interaction of FK506-binding protein 13 with brefeldin A-inhibited guanine nucleotide-exchange protein 1 (BIG1): Effects of FK506
| Autor: | Philip Ian Padilla, Joel Moss, Martha Vaughan, Gustavo Pacheco-Rodriguez, Ronald Adamik, Min-ju Chang |
|---|---|
| Rok vydání: | 2003 |
| Předmět: |
Time Factors
Blotting Western Guanosine Plasma protein binding Jurkat cells Clathrin Tacrolimus Tacrolimus Binding Proteins Jurkat Cells chemistry.chemical_compound symbols.namesake GTP-binding protein regulators GTP-Binding Proteins Two-Hybrid System Techniques Guanine Nucleotide Exchange Factors Humans Cloning Molecular Enzyme Inhibitors Sirolimus Brefeldin A Multidisciplinary Dose-Response Relationship Drug biology Cell Membrane Temperature Biological Sciences Golgi apparatus Precipitin Tests Cell biology Adenosine Diphosphate Biochemistry chemistry Cyclosporine biology.protein symbols Guanine nucleotide exchange factor Immunosuppressive Agents Protein Binding Subcellular Fractions |
| Zdroj: | Proceedings of the National Academy of Sciences. 100:2322-2327 |
| ISSN: | 1091-6490 0027-8424 |
| Popis: | BIG1 and BIG2 are brefeldin A-inhibited guanine nucleotide-exchange proteins that activate ADP-ribosylation factors (ARFs), critical components of vesicular trafficking pathways. These proteins can exist in macromolecular complexes and move between Golgi membranes and cytosol. In the BIG1 molecule, a centrally located Sec7 domain is responsible for ARF activation, but functions of other regions are largely unknown. Yeast two-hybrid screens of a human placenta cDNA library with BIG1 cDNA constructs revealed specific interaction of the N-terminal region (amino acids 1–331) with FK506-binding protein 13 (FKBP13). The association was confirmed by immunoprecipitation of both endogenous BIG1 and FKBP13 from Jurkat T cells with antibodies against either one. Binding of BIG1, BIG2, and ARF to cell membranes in vitro was increased by guanosine 5′-[γ-thio]triphosphate, and further increases were induced by FK506. Incubation of Jurkat T cells with FK506 increased binding of BIG1, BIG2, and ARF to Golgi and other membranes in a time- and concentration-dependent manner, without effects on clathrin or γ-adaptin binding. Binding of BIG1, BIG2, and ARF to membranes was also increased by L-732,531, an agonist structurally related to FK506, but was not increased by a related antagonist, L-685,818, nor by cyclosporin A or rapamycin. These findings are consistent with a role for FKBP13 and FK506 in vesicular trafficking, influencing ARF activity through their guanine nucleotide-exchange proteins. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|