Non-kinase second-messenger signaling: new pathways with new promise
Article first published online: 21 JUN 2004
Copyright © 2004 Wiley Periodicals, Inc.
Volume 26, Issue 7, pages 730–738, July 2004
How to Cite
Springett, G. M., Kawasaki, H. and Spriggs, D. R. (2004), Non-kinase second-messenger signaling: new pathways with new promise. Bioessays, 26: 730–738. doi: 10.1002/bies.20057
- Issue published online: 21 JUN 2004
- Article first published online: 21 JUN 2004
- G.M.S. is an Amos Fellow of the Robert Wood Johnson Foundation and is supported by grants from the American Society of Clinical Oncology and NIH T32CA09207. D.R.S. is supported in part by NIH Grant K24CA087933
Intercellular signaling by growth factors, hormones and neurotransmitters produces second messenger molecules such as cyclic adenosine monophosphate (cAMP) and diacylglycerol (DAG). Protein Kinase A and Protein Kinase C are the principal effector proteins of these prototypical second messengers in certain cell types. Recently, novel receptors for cAMP and DAG have been identified. These proteins, designated EPAC (Exchange Protein directly Activated by cAMP) or cAMP-GEF (cAMP regulated Guanine nucleotide Exchange Factor) and CalDAG-GEF (Calcium and Diacylglycerol regulated Guanine nucleotide Exchange Factor) or RasGRP (Ras Guanine nucleotide Releasing Protein) are able to mediate some of the physiologic effects of the second messengers in a protein-kinase-independent fashion. These proteins are exchange factors for Ras family GTPases that operate in pathways that run parallel to the classic kinase-dependent pathways. The rapidly emerging recognition of the functions of these “non-kinase” effectors in diverse processes such as insulin secretion, thymocyte development, asthma and malignant transformation creates new opportunities for discovery and identifies potential new therapeutic targets. BioEssays 26:730–738, 2004. © 2004 Wiley Periodicals, Inc.