Reinventing the wheel of cyclic AMP: novel mechanisms of cAMP signaling.
Mechanisms of cAMP signal transduction have been thoroughly investigated for more than 40 years. From the binding of hormonal ligands to their receptors on the outer surface of the plasma membrane to the cytoplasmic activation of effectors, the ensuing cAMP signaling cascades and the nuclear gene regulatory functions, coupled with the structural elucidation of the cAMP-dependent protein kinase (PKA) and in vivo functional characterizations of each of the components of PKA by homologous recombination gene targeting, our understanding of cAMP-mediated signal transduction has reached its pinnacle. Despite this trove of knowledge, some recent findings have emerged that suggest hitherto novel and alternative mechanisms of cAMP action that could increase the signaling bandwidth of cAMP and PKA in cell growth and transcriptional regulation. This article attempts to review some of these novel and unconventional mechanisms of cAMP and PKA signaling, and to generate further enthusiasm in investigating and validating these new frontiers of the cAMP signal transduction pathway.
Department of Medicine and Pharmacology and The Cancer Institute of New Jersey, Robert Wood Johnson Medical School, University of Medicine and Dentistry of New Jersey, New Brunswick, New Jersey 08901, USA. chinkv@rwja.umdnj.edu
Khew-Voon
KV
Chin
Weng-Lang
WL
Yang
Roald
R
Ravatn
Tsunekazu
T
Kita
Elena
E
Reitman
David
D
Vettori
Mary Ellen
ME
Cvijic
Michael
M
Shin
Lisa
L
Iacono
D000818:Animals; D002455:Cell Division / Q000502:physiology; D000242:Cyclic AMP / Q000378:metabolism*; D002373:Cyclic AMP Receptor Protein / Q000378:metabolism; D017868:Cyclic AMP-Dependent Protein Kinases / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D051550:I-kappa B Kinase; D007527:Isoenzymes; D016328:NF-kappa B / Q000378:metabolism; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism; D021122:Protein Subunits; D015290:Second Messenger Systems / Q000502:physiology*; D015398:Signal Transduction
D002373:Cyclic AMP Receptor Protein; D007527:Isoenzymes; D016328:NF-kappa B; D021122:Protein Subunits; D000242:Cyclic AMP; D017346:Protein Serine-Threonine Kinases; C496559:CHUK protein, human; D051550:I-kappa B Kinase; C496560:IKBKB protein, human; C496565:IKBKE protein, human; D017868:Cyclic AMP-Dependent Protein Kinases