| | |  | | | | Record from Web of Science® | | | | | | |
| PHOSPHORYLATION OF CREB AFFECTS ITS BINDING TO HIGH AND LOW AFFINITY SITES - IMPLICATIONS FOR CAMP INDUCED GENE-TRANSCRIPTION |
|
|
| Author(s): NICHOLS M, WEIH F, SCHMID W, DEVACK C, KOWENZLEUTZ E, LUCKOW B, BOSHART M, SCHUTZ G |
| Source: EMBO JOURNAL Volume: 11 Issue: 9 Pages: 3337-3346 Published: SEP 1992 |
| Times Cited: 271 References: 58 |
| Abstract: Cyclic AMP treatment of hepatoma cells leads to increased protein binding at the cyclic AMP response element (CRE) of the tyrosine aminotransferase (TAT) gene in vivo, as revealed by genomic footprinting, whereas no increase is observed at the CRE of the phosphoenolpyruvate carboxykinase (PEPCK) gene. Several criteria establish that the 43 kDa CREB protein is interacting with both of these sites. Two classes of CRE with different affinity for CREB are described. One class, including the TATCRE, is characterized by asymmetric and weak binding sites (CGTCA), whereas the second class containing symmetrical TGACGTCA sites shows a much higher binding affinity for CREB. Both classes show an increase in binding after phosphorylation of CREB by protein kinase A (PKA). An in vivo phosphorylation-dependent change in binding of CREB increases the occupancy of weak binding sites used for transactivation, such as the TATCRE, while high affinity sites may have constitutive binding of transcriptionally active and inactive CREB dimers, as demonstrated by in vivo footprinting at the PEPCK CRE. Thus, lower basal level and higher relative stimulation of transcription by cyclic AMP through low affinity CREs should result, allowing finely tuned control of gene activation. |
| Document Type: Article |
| Language: English |
| Reprint Address: NICHOLS, M (reprint author), GERMAN CANC RES CTR, INST CELL & TUMOR BIOL, NEUENHEIMER FELD 280, W-6900 HEIDELBERG, GERMANY |
| Publisher: OXFORD UNIV PRESS UNITED KINGDOM, WALTON ST JOURNALS DEPT, OXFORD, ENGLAND OX2 6DP |
| Subject Category: Biochemistry & Molecular Biology; Cell Biology |
| IDS Number: JJ039 |
| ISSN: 0261-4189 |
|
| | | | | | | | | Record from Web of Science® | | | | | | | | | |