PMID- 8769368
OWN - NLM
STAT- MEDLINE
DCOM- 19961210
LR  - 20220330
IS  - 0026-0495 (Print)
IS  - 0026-0495 (Linking)
VI  - 45
IP  - 8 Suppl 1
DP  - 1996 Aug
TI  - Regulation of somatostatin gene transcription by cyclic adenosine monophosphate.
PG  - 4-7
AB  - Cyclic adenosine monophosphate (cAMP) stimulates transcription of somatostatin 
      and other target genes with burst-attenuation kinetics. The kinetics of protein 
      kinase (PK-A)-dependent cAMP response element binding protein (CREB) 
      phosphorylation closely parallel the changes in transcription of cAMP-responsive 
      genes by run-on assay. Nuclear translocation of PK-A, visualized by 
      microinjection of fluorescently labeled PK-A holoenzyme, appears to represent the 
      rate-limiting step in CREB phosphorylation and transcriptional activation. We and 
      others have recently characterized a CREB-binding protein (CBP), which 
      specifically recognizes sequences within the Ser133 phosphorylated form of CREB. 
      CBP does not regulate the DNA binding, dimerization, or nuclear targeting 
      properties of CREB, but binds selectively to the kinase-inducible 60 amino acid 
      trans-activation domain (KID) of CREB, critical for PK-A-inducible transcription. 
      We developed an antiserum directed against amino acid 634-648 within the 
      CREB-binding domain of CBP. We detected a 265-kd polypeptide by Western blot as 
      predicted from the cDNA, which coincided with the predominant 
      phospho-CREB-binding activity in Hela nuclear extracts by "Far Western" blot 
      assay. An identical phospho-CREB-binding activity was also found in NIH-3T3 
      cells. This phospho-CREB-binding protein appeared to be specific for 
      Ser133-phosphorylated CREB, because no such band was detected with CREB labeled 
      to the same specific activity at a nonregulatory phosphoacceptor site (Ser156) by 
      casein kinase II (CKII). Following microinjection into nuclei of NIH-3T3 cells, a 
      cAMP response element (CRE)-lacZ reporter was markedly induced by treatment with 
      8-Br cAMP plus isobutyl methyl xanthine (IBMX). Coinjection of CBP antiserum with 
      the CRE-lacZ plasmid inhibited cAMP-dependent activity in a dose-dependent 
      manner, but control immunoglobulin G (lgG) had no effect on this response. We can 
      now begin reconstituting PK-A-dependent transcription in vitro, using 
      well-characterized proteins such as CREB, TAF 110, and CBP. The assembly of such 
      factors on cAMP-regulated promoters like somatostain may enable responsiveness to 
      a variety of hormonal stimuli that employ cAMP as their second messenger.
FAU - Montminy, M
AU  - Montminy M
AD  - Clayton Foundation Laboratories for Peptide Biology, Salk Institute, La Jolla, CA 
      92037, USA.
FAU - Brindle, P
AU  - Brindle P
FAU - Arias, J
AU  - Arias J
FAU - Ferreri, K
AU  - Ferreri K
FAU - Armstrong, R
AU  - Armstrong R
LA  - eng
GR  - GM37828/GM/NIGMS NIH HHS/United States
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Research Support, U.S. Gov't, P.H.S.
PT  - Review
PL  - United States
TA  - Metabolism
JT  - Metabolism: clinical and experimental
JID - 0375267
RN  - 0 (Cyclic AMP Response Element-Binding Protein)
RN  - 0 (Immune Sera)
RN  - 0 (Nuclear Proteins)
RN  - 0 (Trans-Activators)
RN  - 0 (Transcription Factors)
RN  - 51110-01-1 (Somatostatin)
RN  - E0399OZS9N (Cyclic AMP)
RN  - EC 2.3.1.48 (CREB-Binding Protein)
RN  - EC 2.3.1.48 (CREBBP protein, human)
RN  - EC 2.3.1.48 (Crebbp protein, mouse)
RN  - EC 2.7.11.11 (Cyclic AMP-Dependent Protein Kinases)
SB  - IM
MH  - 3T3 Cells
MH  - Animals
MH  - Blotting, Western
MH  - CREB-Binding Protein
MH  - Cyclic AMP/*physiology
MH  - Cyclic AMP Response Element-Binding Protein/metabolism
MH  - Cyclic AMP-Dependent Protein Kinases/metabolism
MH  - HeLa Cells
MH  - Humans
MH  - Immune Sera
MH  - Mice
MH  - Nuclear Proteins/metabolism
MH  - Phosphorylation
MH  - Precipitin Tests
MH  - Somatostatin/*genetics
MH  - *Trans-Activators
MH  - Transcription Factors/metabolism
MH  - Transcription, Genetic/*physiology
RF  - 12
EDAT- 1996/08/01 00:00
MHDA- 1996/08/01 00:01
CRDT- 1996/08/01 00:00
PHST- 1996/08/01 00:00 [pubmed]
PHST- 1996/08/01 00:01 [medline]
PHST- 1996/08/01 00:00 [entrez]
AID - S0026-0495(96)90068-2 [pii]
AID - 10.1016/s0026-0495(96)90068-2 [doi]
PST - ppublish
SO  - Metabolism. 1996 Aug;45(8 Suppl 1):4-7. doi: 10.1016/s0026-0495(96)90068-2.