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Protein Kinase A: The Enzyme and Cyclic AMP Signaling

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Post-Translational Modifications in Health and Disease

Part of the book series: Protein Reviews ((PRON,volume 13))

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Abstract

The main target of cAMP action in the cell is cAMP-dependent protein kinase (PKA) which exists mainly as two different isozymes, designated as type I (PKA-I) and type II (PKA-II) (more isozymes may exist). The two isoforms are distinct in their physico-chemical properties; the unexpectedly great differences between two isoforms of the same kinase that are both under tight control by the cAMP molecule point to an isozyme-specific involvement of PKA in cell functions. The relative ratio of PKA-I and PKA-II varies not only throughout the cell cycle in cells of the same type, but also among cells of the same tissue, and depends on developmental and differentiation stages. The balance of expression between PKA-I and PKA-II possibly plays a critical role as a sensitive regulator of cell growth, proliferation, and differentiation. Inactivating mutations of the gene coding for PKA-I regulatory subunit RIα (PRKAR1A) were found in a human disease (Carney Complex) that is linked to an inherited predisposition to a variety of largely benign and few malignant tumors; this finding further strengthened the notion that the holoenzyme’s function is critical for cellular growth and proliferation in at least the cAMP-responsive tissues. Thus, PKA has also emerged as a possible therapeutic target; its activity can be modulated with analogs of cAMP, oligonucleotides (antisense, transcription decoy oligonucleotide) and other agents targeting protein partners in signaling pathways. The first results of experiments with PKA modulators encouraged researchers to investigate further a new approach to therapy in the treatment of diseases using relatively nontoxic agents that are able to restore the natural balance of proliferation and differentiation in cells.

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Acknowledgments

This work was supported by NICHD, NIH intramural project Z01-HD-000642-04 to Dr. C.A. Stratakis.

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  1. Section on Endocrinology Genetics, Program on Developmental Endocrinology Genetics (PDEGEN), Eunice Kenney Shriver National Institute of Child Health & Human Development (NICHD), National Institute of Health (NIH), Building 10, CRC (East Laboratories), Room 1-3330, 10 Center Dr., MSC1103, Bethesda, MD, 20892, USA

    Constantine A. Stratakis

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  1. Maria Nesterova
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  1. Depto. Quimica Inorganica, Universidad Murcia, Murcia, Spain

    Cecilio J. Vidal

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Nesterova, M., Stratakis, C.A. (2011). Protein Kinase A: The Enzyme and Cyclic AMP Signaling. In: Vidal, C. (eds) Post-Translational Modifications in Health and Disease. Protein Reviews, vol 13. Springer, New York, NY. https://doi.org/10.1007/978-1-4419-6382-6_7

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