scholarly journals Phosphorylation of Conserved Casein Kinase Sites Regulates cAMP-response Element-binding Protein DNA Binding inDrosophila

2003 ◽  
Vol 279 (13) ◽  
pp. 12117-12125 ◽  
Author(s):  
Junjiro Horiuchi ◽  
Wei Jiang ◽  
Hong Zhou ◽  
Priscilla Wu ◽  
Jerry C. P. Yin
Keyword(s):  
Dna Binding ◽  
Binding Protein ◽  
Camp Response Element Binding ◽  
Casein Kinase ◽  
Camp Response Element ◽  
Response Element ◽  
Element Binding Protein

scholarly journals Identification and Functional Analysis of the Novel S179R POU1F1 Mutation Associated with Combined Pituitary Hormone Deficiency

2006 ◽  
Vol 91 (12) ◽  
pp. 4981-4987 ◽  
Author(s):  
Ichiro Miyata ◽  
Sophie Vallette-Kasic ◽  
Alexandru Saveanu ◽  
Mizuho Takeuchi ◽  
Hideki Yoshikawa ◽  
...  
Keyword(s):  
Transcription Factor ◽  
Dna Binding ◽  
Binding Protein ◽  
Camp Response Element Binding ◽  
Hormone Deficiency ◽  
Nuclear Accumulation ◽  
Pituitary Hormone ◽  
Camp Response Element ◽  
Response Element ◽  
Element Binding Protein

Abstract Context: The pituitary-specific transcription factor 1 plays a key role in the development and differentiation of three pituitary cell types: somatotrophs, lactotrophs, and thyrotrophs. Several mutations of the human gene (called POU1F1) have been shown to be responsible for a phenotype of combined pituitary hormone deficiency involving GH, prolactin (PRL), and TSH. Objective: We have identified a novel homozygous C to G mutation in exon 4 of the POU1F1 gene (S179R) in a patient with this rare phenotype. We analyzed the functional consequences of this S179R mutation associated with a single-amino acid change in the POU-specific domain. Methods: Consequences of this mutation on transcriptional activities by transfection studies in αT3 cells, DNA binding ability by EMSA, structural properties, and nuclear accumulation of POU1F1 were investigated. Results: The transactivation capacity of this mutant was markedly decreased on the GH1, PRL, TSHβ, and POU1F1 genes. Interestingly, this mutation abolished the functional interaction of POU1F1 on the PRL promoter with the coactivator cAMP response element-binding protein-binding protein but not with the transcription factor LIM homeodomain transcription factor 3. The S179R mutant displayed normal nuclear accumulation but a markedly decreased binding to a DNA response element in keeping with crystallographic data, suggesting that the S179R mutation might interfere with DNA binding. Conclusions: Together with previous data, our study indicates that both DNA binding and interaction with cofactors like cAMP response element-binding protein-binding protein are critical for POU1F1 function and that functional and structural properties of abnormal POU1F1 proteins are variously influenced by the type of mutations.

scholarly journals Cell-cycle-regulated phosphorylation of cAMP response element-binding protein: identification of novel phosphorylation sites

1999 ◽  
Vol 338 (1) ◽  
pp. 49-54 ◽  
Author(s):  
Kumiko SAEKI ◽  
Akira YUO ◽  
Fumimaro TAKAKU
Keyword(s):  
Cell Cycle ◽  
Protein Identification ◽  
Binding Protein ◽  
Consensus Sequence ◽  
Casein Kinase Ii ◽  
Camp Response Element Binding ◽  
Casein Kinase ◽  
Camp Response Element ◽  
Response Element ◽  
Element Binding Protein

We report that the cAMP response element binding protein (CREB) undergoes cell-cycle-regulated phosphorylation. In human amnion FL cells, CREB was expressed as two forms with different molecular masses, 45 and 45.5 kDa. Although asynchronous cells contained predominantly the 45 kDa forms, this form shifted to 45.5 kDa when the cells were synchronized with the early S-phase. Furthermore the expression of the 45.5 kDa band was increased when cells were treated with okadaic acid, confirming that the 45.5 kDa band was a phosphorylated form of the 45 kDa band. Mutation analysis indicated that neither Ser133, the target of cAMP-dependent protein kinase and calcium calmodulin kinase, nor Ser129, the target of glycogen synthetase kinase 3, was responsible for the expression of the 45.5 kDa band, but that Ser108, Ser111 and Ser114, located in a region matching the consensus sequence for the casein kinase II target, were required. A mutant in which Ser111 and Ser114 were each replaced by a glutamic residue, mimicking a phosphorylated state, had a higher activation potential in cAMP response element-mediated transcription. These results strongly suggest that the casein kinase II target region is involved in cell cycle-regulated phosphorylation of the CREB protein and also in transcriptional enhancement.

Scutellarin Mitigates Cancer-Induced Bone Pain by Suppressing CaMKII/CREB Pathway in Rat Models

2019 ◽  
Vol 17 (3) ◽  
pp. 249-253
Author(s):  
Liu Chenglong ◽  
Liu Haihua ◽  
Zhang Fei ◽  
Zheng Jie ◽  
Wei Fang
Keyword(s):  
Protein Kinase ◽  
Bone Pain ◽  
Binding Protein ◽  
Camp Response Element Binding ◽  
Camp Response Element ◽  
Dependent Protein Kinase ◽  
Response Element ◽  
Protein Kinase Ii ◽  
Element Binding Protein ◽  
Dependent Protein

Cancer-induced bone pain is a severe and complex pain caused by metastases to bone in cancer patients. The aim of this study was to investigate the analgesic effect of scutellarin on cancer-induced bone pain in rat models by intrathecal injection of Walker 256 carcinoma cells. Mechanical allodynia was determined by paw withdrawal threshold in response to mechanical stimulus, and thermal hyperalgesia was indicated by paw withdrawal latency in response to noxious thermal stimulus. The paw withdrawal threshold and paw withdrawal latencies were significantly decreased after inoculation of tumor cells, whereas administration of scutellarin significantly attenuated tumor cell inoculation-induced mechanical and heat hyperalgesia. Tumor cell inoculation-induced tumor growth was also significantly abrogated by scutellarin. Ca2+/calmodulin-dependent protein kinase II is a multifunctional kinase with up-regulated activity in bone pain models. The activation of Ca2+/calmodulin-dependent protein kinase II triggers phosphorylation of cAMP-response element binding protein. Scutellarin significantly reduced the expression of phosphorylated-Ca2+/calmodulin-dependent protein kinase II and phosphorylated-cAMP-response element binding protein in cancer-induced bone pain rats. Collectively, our study demonstrated that scutellarin attenuated tumor cell inoculation-induced bone pain by down-regulating the expression of phosphorylated-Ca2+/calmodulin-dependent protein kinase II and phosphorylated-cAMP-response element binding protein. The suppressive effect of scutellarin on phosphorylated-Ca2+/calmodulin-dependent protein kinase II/phosphorylated-cAMP-response element binding protein activation may serve as a novel therapeutic strategy for CIBP management.

cAMP Response Element Binding Protein Is Expressed and Phosphorylated in the Human Heart

Circulation ◽  
1995 ◽  
Vol 92 (8) ◽  
pp. 2041-2043 ◽  
Author(s):  
Frank Ulrich Müller ◽  
Peter Bokník ◽  
Andreas Horst ◽  
Jörg Knapp ◽  
Bettina Linck ◽  
...  
Keyword(s):  
Human Heart ◽  
Binding Protein ◽  
Camp Response Element Binding ◽  
Camp Response Element ◽  
Response Element ◽  
Element Binding Protein
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