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Non‐kinase second‐messenger signaling: new pathways with new promise
Author(s) -
Springett Gregory M.,
Kawasaki Hiroaki,
Spriggs David R.
Publication year - 2004
Publication title -
bioessays
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.175
H-Index - 184
eISSN - 1521-1878
pISSN - 0265-9247
DOI - 10.1002/bies.20057
Subject(s) - guanine nucleotide exchange factor , second messenger system , diacylglycerol kinase , protein kinase a , microbiology and biotechnology , biology , protein kinase c , effector , signal transduction , biochemistry , kinase
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 ( E xchange P rotein directly A ctivated by c AMP) or cAMP‐GEF (cAMP regulated G uanine nucleotide E xchange F actor) and CalDAG‐GEF ( C alcium and D i a cyl g lycerol regulated G uanine nucleotide E xchange F actor) or RasGRP (Ras G uanine nucleotide R eleasing P rotein) 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.