IBYME   02675
INSTITUTO DE BIOLOGIA Y MEDICINA EXPERIMENTAL
Unidad Ejecutora - UE
artículos
Título:
3. Regulatory mechanisms underlying GKR2 levels in U937 cells. Evidence for GRK3 involvement
Autor/es:
NATALIA FERNANDEZ, FEDERICO MONCZOR, MARIA R TUBIO, CARINA SHAYO, AND CARLOS DAVIO.
Revista:
BIOCHEMICAL PHARMACOLOGY
Referencias:
Año: 2007 vol. 73 p. 1758 - 1767
ISSN:
0006-2952
Resumen:
G protein-coupled receptors represent the most diverse group of proteins involved in
transmembrane signalling, that participate in the regulation of a wide range of physicochemical
messengers through the interaction with heterotrimeric G proteins. In addition,
GPCRs stimulation also triggers a negative feedback mechanism, known as desensitization
that prevents the potentially harmful effects caused by persistent receptor stimulation. In
this adaptative response, G protein-coupled receptor kinases (GRKs) play a key role and
alterations in their function are related to diverse pathophysiological situations. Based on
the scarce knowledge about the regulation of GRK2 by other kinases of the same family, the
aim of the present work was to investigate the regulation of GRK2 levels in systems where
other GRKs are diminished by antisense technique. Present findings show that in U937 cells
GRK2 levels are regulated by GRK3 and not by GRK6 through a mechanism involving InsP
upregulation. This work reports a novel GRK3-mediated GRK2 regulatory mechanism and
further suggests that GRK2 may also act as a compensatory kinase tending to counterbalance
the reduction in GRK3 levels. This study provides the first evidence for the existence
of GRKs cross-regulation.