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The Ways in Which Hormones Change Cyclic Adenosine 3',5'-Monophosphate-Dependent Protein Kinase Subunits, and How Such Changes Affect Cell Behavior^*

Medical Research Service, Buffalo VAMC and Department of Medicine SUNYAB, Buffalo, New York 14215

Correspondence: Address requests for reprints to: Stephen W. Spaulding, M.D., Medical Research Service, Buffalo Veterans Affairs Medical Center and Department of Medicine, State University of New York at Buffalo, 3495 Bailey Avenue, Buffalo, New York 14215.

Abstract

HORMONES and cytokines regulate many cellular functions by activating the ubiquitous cAMP-pendent protein kinase (A kinase) system. Newly synthesized cAMP molecules bind to regulatory (R) subunits in A kinase holoenzymes, causing them to release their catalytic (C) subunits. These free C subunits then phosphorylate proteins until the cAMP level falls, whereupon the R subunits regain their affinity for free C subunits, and thus form inactive holoenzymes again. However if cAMP levels remain persistently elevated, many cells change their A kinase system. Some cells alter the rate of degradation of subunits, and some cells change the level or stability of the messages encoding subunits. Cellular behavior often changes if cAMP levels remain elevated: many cells differentiate, some cells proliferate, and some cells die, depending on the stage of the cell cycle.

The two forms of A kinase holoenzyme (type I and type II) contain identical C subunits, but contain either an RI dimer or an RII dimer. In some tissues, type II holoenzyme is compartmentalized to subcellular organelles via specific anchoring proteins, whereas type I holoenzyme is generally cytosolic. Free RI subunits turn over more rapidly than free RII subunits in most cells, but all free subunits are degraded more rapidly than when they are associated together in holoenzymes.

Footnotes

^* Supported by Veterans Administration Medical Research funds.

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