REGULATION OF G-PROTEIN-COUPLED RECEPTOR KINASE SUBTYPES IN ACTIVATEDT-LYMPHOCYTES - SELECTIVE INCREASE OF BETA-ADRENERGIC-RECEPTOR KINASE-1 AND KINASE-2
A. Deblasi et al., REGULATION OF G-PROTEIN-COUPLED RECEPTOR KINASE SUBTYPES IN ACTIVATEDT-LYMPHOCYTES - SELECTIVE INCREASE OF BETA-ADRENERGIC-RECEPTOR KINASE-1 AND KINASE-2, The Journal of clinical investigation, 95(1), 1995, pp. 203-210
beta-adrenergic receptor kinase (beta ARK) is a serine-threonine kinas
e involved in the process of homologous desensitization of G-coupled r
eceptors. beta ARK is a member of a multigene family, consisting of si
x known subtypes, also named G protein-coupled receptor kinases (GRK 1
-6), In this study we investigated the expression of GRKs during the p
rocess of T cell activation, which is of fundamental importance in reg
ulating immune responses. T cell activation was induced by exposing mo
nonuclear leukocytes (MNL) to PHA and confirmed by tritiated thymidine
incorporation measurement, A substantial increase of GRK activity (as
measured by in vitro phosphorylation of rhodopsin) was found after 48
h (331+/-80% of controls) and 72 h (347+/-86% of controls) of exposur
e to PHA. A threefold increase of beta ARK1 immunoreactivity was found
in MNL exposed to PHA for 72 h. Persistent activation of protein kina
se C (PKC) by 10 nM 12-O-tetradecanoylphorbol-13-acetate (TPA) was abl
e to increase beta ARK activity to the same extent as PHA, suggesting
a PKC-mediated mechanism. The kinetic of beta-adrenergic-stimulated cA
MP production was substantially modified in TPA and PHA-activated cell
s, indicating that the increased GRK activity resulted in an increased
beta-adrenergic homologous desensitization. A three- to fourfold incr
ease in GRK activity was also observed in a population of T cell blast
s (> 97% CD3+) exposed to PHA for 48-72 h. A significant increase in b
eta ARK1 and beta ARK2 mRNA expression was observed 48 h after mitogen
stimulation, while mRNA expression of GRK5 and GRK6 was not changed,
In conclusion our data show that the expression of GRK subtypes is act
ively and selectively modulated according to the functional state of T
lymphocytes.