Phosphorylase kinase: the complexity of its regulation is reflected in the complexity of its structure

Differentiation-dependent mechanisms of transcriptional regulation of the catalytic subunit of phosphorylase kinase

“…This degree of complexity mirrors the complexity of the PhK protein [1] and therefore is not surprising. Already we know of an elaborate set of covalent and allosteric controls that modulate PhK catalytic activity.…”

“…PhK is a protein the complexity of regulation of which matches its complexity of structure, and it is the site of integration of multiple signal-transduction pathways [1,2]. While currently its only established function is the regulation of glycogenolysis, the discovery of other physiologically important roles appears likely [1].…”

“…While currently its only established function is the regulation of glycogenolysis, the discovery of other physiologically important roles appears likely [1]. It is now evident that the basis for regulation of the catalytic activity of broad categories of the protein kinase family of enzymes is that of suppression of the inherent endogenous activity of the catalytic domain.…”

“…This hexadecameric enzyme, with subunit composition (αβγδ) % , serves to integrate both hormonal and neuronal signals, leading to the breakdown of intracellular glycogen stores [1,2]. Physiological activation of the holoenzyme occurs as a result of either the phosphorylation of the α and β subunits by the cAMP-dependent protein kinase and\or the binding of Ca# + to the intrinsic calmodulin subunit (i.e., δ).…”

“…These various covalent and allosteric modifications of the α, β and δ regulatory subunits are thought to induce a conformational change in the protein that relieves their inhibition of the γ catalytic subunit. Within the PhK holoenzyme these regulatory mechanisms are tightly integrated as a consequence of subunitsubunit interactions (see [1,2] and references cited therein).…”