A region in the cytosolic domain of the epidermal growth factor receptor antithetically regulates the stimulatory and inhibitory guanine nucleotide-binding regulatory proteins of adenylyl cyclase
| Autor: | Tarun B. Patel, Jerome M. Seyer, Hui Sun |
|---|---|
| Rok vydání: | 1995 |
| Předmět: |
G protein
Molecular Sequence Data GTPase Biology GTP Phosphohydrolases Adenylyl cyclase chemistry.chemical_compound Cytosol GTP-binding protein regulators GTP-Binding Proteins Epidermal growth factor Escherichia coli Animals Amino Acid Sequence Cloning Molecular Phosphorylation Peptide sequence Protein kinase C Multidisciplinary Brain Peptide Fragments Recombinant Proteins ErbB Receptors Kinetics chemistry Biochemistry Guanosine 5'-O-(3-Thiotriphosphate) Cattle Guanosine Triphosphate Research Article Adenylyl Cyclases |
| Zdroj: | Proceedings of the National Academy of Sciences. 92:2229-2233 |
| ISSN: | 1091-6490 0027-8424 |
| Popis: | Epidermal growth factor (EGF) stimulates adenylyl cyclase in the heart via activation of the stimulatory GTP-binding protein Gs. Therefore, employing peptides corresponding to regions in the cytosolic domain of the EGF receptor, we have investigated the ability of sequences within the EGF receptor to activate Gs. A 13-aa peptide (EGFR-13) corresponding to the juxtamembrane region in the cytosolic domain of the EGF receptor stimulated GTP binding and GTPase activity of Gs. This peptide did not stimulate GTP binding to Gi but increased the GTPase activity of this protein. Additionally, phosphorylation of the protein kinase C site (threonine residue) within EGFR-13 decreased the ability of the peptide to stimulate Gs and increase GTPase activity of Gi. Further, in functional assays of Gs employing S49 cyc- cell membranes, EGFR-13 increased the ability of Gs to stimulate adenylyl cyclase; phospho-EGFR-13 and a 14-aa peptide corresponding to a sequence in the cytosolic domain of the EGF receptor did not alter the functional activity of Gs. Hence, the juxtamembrane region of the EGF receptor can activate Gs and, by stimulating GTPase activity of Gi, inactivates this latter G protein. Phosphorylation of the threonine residue within this region attenuates the activity of the peptide as a modulator of G-protein function. |
| Databáze: | OpenAIRE |
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