|MadSci Network: Cell Biology|
Hello. 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:// www.ncbi.nlm.nih.gov/PubMed). 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, 1996). This all gets quite complicated and there is a lot of other literature out there. I hope this information helps. Luke. References: 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). 2001
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