Reinventing the wheel of cyclic AMP: novel mechanisms of cAMP signaling

• Published in: Annals of the New York Academy of Sciences 2002-06, Vol.968 (1), p.49-64
• Main Authors: Chin, Khew-Voon, Yang, Weng-Lang, Ravatn, Roald, Kita, Tsunekazu, Reitman, Elena, Vettori, David, Cvijic, Mary Ellen, Shin, Michael, Iacono, Lisa
• Format: Article
• Language: English
• Subjects: Animals; Cell Division - physiology; Cyclic AMP - metabolism; Cyclic AMP Receptor Protein - metabolism; Cyclic AMP-Dependent Protein Kinases - genetics; Cyclic AMP-Dependent Protein Kinases - metabolism; Humans; I-kappa B Kinase; Isoenzymes; NF-kappa B - metabolism; Protein Subunits; Protein-Serine-Threonine Kinases - metabolism; Second Messenger Systems - physiology; Signal Transduction
• ISSN: 0077-8923; 1749-6632
• DOI: 10.1111/j.1749-6632.2002.tb04326.x

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.