MadSci Network: Cell Biology

Re: what is C/EBP and how does PKA affect it?

Date: Sat Mar 9 23:54:01 2002
Posted By: Luke Collyer, Graduate Student, Biochemistry & Molecular Biology, Monash University
Area of science: Cell Biology
ID: 1015445956.Cb


Wow. What a question. Firstly, I must tell you I know little about C/EBP. 
However, here is some information I got from a PubMed search (http:// 

C/EBP stands for CCAAT/enhancer binding protein. The C/EBP family of 
proteins consists of 6 members. C/EBP-alpha was the first to be 
characterised. Knockout studies in mice have found C/EBP-alpha to be 
essential in hepatocyte (liver cell) and adipocyte (fat cell) 
differentiation. (see Lekstrom-Himes, 2001)

Now the link to PKA....

Cyclic-AMP (cAMP) is an important intracellular signalling molecule that 
among other things, leads to the transcriptional activation of a number of 
genes. cAMP generally exerts its effects in cells via the activation of 
protein kinase A (PKA). Protein kinase A catalyses the transfer of the 
terminal phosphate group of ATP to specific serine and threonine residues 
within select proteins, such as transcription factors. 

The somatostatin (a peptide hormone) gene is an example of gene that is 
transcriptionally regulated by cAMP. Within the regulatory region of the 
somatostatin gene exists a short DNA sequence called a cAMP response 
element (CRE). This DNA sequence in recognised by the gene regulatory 
protein CRE-binding (CREB) protein. When PKA phosphorylates CREB at a 
specific serine residue, the CREB becomes activated, leading to the 
transcriptional activation of CREB regulated genes (Alberts et. al., 1994). 

Now, cAMP-mediated regulation of C/EBP-beta and C/EBP-delta has been 
reported by one group (Cardinaux and Magistretti, 1996), and a cAMP 
response element (CRE) has been identified in the promoter region of 
C/EBP-delta (Cantwell et. al., 1998). Therefore C/EBP-delta expression may 
be regulated by cAMP via PKA and CREB proteins. Finally, a number of serine 
targets of PKA have been identified in C/EBP-beta, suggesting its 
activities are post-translationally regulated by cAMP (Brasier and Li, 

This all gets quite complicated and there is a lot of other literature out 
there. I hope this information helps. 



Alberts B, Bray, D, Lewis J, Raff M, Roberts K, and Watson JD. Molecular   
Biology of the Cell, Garland Publishing, NY (1994)

Brasier AR,  and Li J. Mechanisms for Inducible Control of Angiotensinogen 
Gene Transcription. Hypertension 27:465-475 (1996).

Cantwell CA, Sterneck E, Johnson PF. Interleukin-6-Specific Activation of 
the C/EBP Delta Gene in Hepatocytes is mediated by Stat3 and Sp1. Mol. 
Cell. Biol. 18:2108-2117 (1998).

Cardinauz JR, and Magistretti PJ. Vasoactive Intestinal Peptide, Pituitary 
Adenylate Cyclase-Activating Peptide, and Noradrenaline Induce the 
Transcription factors CCAAT/Enhancer Binding Protein (C/EBP)-beta and 
C/EBP-delta in Mouse Cortical Astrocytes: Involvement in cAMP-regulated 
Glycogen Metabolism. J. Neurosci. 16:919-929 (1996).

Lekstrom-Himes, JA. The Role of C/EBP-epsilon in the Terminal Stages of 
Granulocyte Differentiation. Stem Cells, 19:125-133 (2001).

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