The role of calcium ions (Ca2+) in cell function is beginning to be unraveled at the molecular level as a result of recent research on calcium-binding proteins and particularly on calmodulin. These proteins interact reversibly with Ca2+ to form a protein . Ca2+ complex, whose activity is regulated by the cellular flux of Ca2+. Many of the effects of Ca2+ appear to be exerted through calmodulin-regulated enzymes.

Calmodulin plays a pivotal role in cellular regulation

Protein phosphorylation is now recognized to be the major general mechanism by which intracellular events in mammalian tissues are controlled by external physiological stimuli However, only recently has the idea that different cellular functions are controlled by common protein kinases and protein phosphatases started to gain widespread acceptance Thus there is an integrated network of regulatory pathways, mediated by phosphorylation-dephosphorylation, that allows diverse cellular events to be coordinated by neural and hormonal stimuli The evidence that supports this concept is reviewed, with emphasis on the role of protein phosphorylation in enzyme regulation

The role of protein phosphorylation in neural and hormonal control of cellular activity

The hypothesis advanced in this article requires further validation. Undoubtedly it will require modification as our knowledge of biochemical control increases. Nevertheless, it should prove useful in focusing attention on the apparent similarity in the response of a large number of specific cell types to particular stimuli. Emphasis has been placed on a few common and apparently key elements in these responses. It is recognized that other factors are undoubtedly involved. Specifically, the changes in membrane potentials indicate the likelihood of widespread changes in the properties of the cell membrane, for example, changes in Na(+) and K(+) transport and distribution. These aspects of cellular responses may eventually prove to be of equal or greater importance than those common aspects of the system already identified.

Cell Communication, Calcium Ion, and Cyclic Adenosine Monophosphate

The reversible phosphorylation of proteins is central to the regulation of most aspects of cell function but, even after the first protein kinase was identified, the general significance of this discovery was slow to be appreciated. Here I review the discovery of protein phosphorylation and give a personal view of the key findings that have helped to shape the field as we know it today.

Edwin G. Krebs

Papers

Comparison of adenosine 3':5'-monophosphate-dependent protein kinases from rabbit skeletal and bovine heart muscle.

The regulation of skeletal muscle phosphorylase kinase by Ca2

Purification and characterization of catalytic subunit of skeletal muscle adenosine 3':5'-monophosphate-dependent protein kinase.

Concentrations of cyclic AMP-dependent protein kinase subunits in various tissues.

Separation of regulatory and catalytic subunits of the cyclic 3′, 5′-adenosine monophosphate-dependent protein kinase(s) of rabbit skeletal muscle