Non-kinase second-messenger signaling: new pathways with new promise

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 CaIDAG-GEF (Calcium and Diacylglycerol regulated Guanine nucleotide Exchange Factor) or RasGRP (Ras Guanine nucleotide Releasing Protein) ate able to mediate some of the physiologic effects of the second messengers in a protein-kinase-independent fashion. These proteins are exchange factors foe 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. (C) 2004 Wiley Periodicals, Inc.