Article,
G-protein-coupled receptor kinases
Kidney Int, 49 (4): 1047-52 (April 1996)Lohse, M J Krasel, C Winstel, R Mayor, F Jr Research Support, Non-U.S. Gov't Review United states Kidney international Kidney Int. 1996 Apr;49(4):1047-52..
Abstract
beta-Adrenergic receptors are prototypes of the many G-protein-coupled
receptors. Activation and inactivation of these receptors are regulated
by multiple mechanisms which can affect either their function or
their expression. The most obvious changes of such receptor systems
are induced by activation of the receptors themselves by their respective
agonists, and this process is called receptor desensitization. One
of these mechanisms of desensitization is due to the actions of specific
receptor kinases, termed the G-protein-coupled receptor kinases (GRKs).
These kinases specifically phosphorylate only the agonist-occupied
form of such receptors. This phosphorylation is then followed by
binding of inhibitor proteins, called arrestins, to the receptors.
Binding of arrestins results in displacement of the G-proteins from
the receptors and hence causes uncoupling of receptors and G-proteins.
Recent data indicate that the function and subcellular distribution
of GRKs is itself subject to regulation. Various mechanisms have
evolved to anchor the different GRKs to the plasma membrane. In addition,
recent data indicate that GRKs can also associate with intracellular
membranes where they may exert as yet unknown functions. A pathophysiological
role for GRKs can be inferred from recent studies on heart failure
as well as the observation that chronic treatment with various agonists
or antagonists for G-protein-coupled receptors results in alterations
of GRK expression.
