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P. PENELA Y COLS. AN. R. ACAD. NAC. FARM

FIGURE 1.- GRK2 functionally interacts with multiple signalling proteins involved in cell
migration. See text for details.

GRK2 STRUCTURE AND MODULATION

GRK family members can be subdivided into three main groups
based on sequence homology: rhodopsin kinase or visual GRK subfamily
(GRK1 and GRK7), the ß-adrenergic receptor kinase subfamily
(GRK2/GRK3) and the GRK4 subfamily (GRK4, GRK5 and GRK6).
GRK2, 3, 5 and 6 are ubiquitously expressed in mammalian tissues.

GRKs share a common structural architecture with a well-
conserved, central catalytic domain (~270 aa), similar to that of other
serine-threonine kinases, flanked by an N-terminal domain (~185 aa) and a
variable-length carboxyl-terminal domain (~105-230 aa). The N-terminal
domain has been proposed to be important for receptor recognition, for
intracellular membrane anchoring and also contains an RH domain
(regulator of G protein signalling homology domain) of ~120 aa. In the
case of GRK2 and GRK3, the RH domain has been shown to specifically
interact with Gaq family members, thus blocking its interaction with their
effector phospholipase C beta. The C-terminal region of GRK2 contains a
pleckstrin homology domain (PH) with binding sites for the membrane
phospholipid PIP2 and free Gß? subunits and therefore is involved in its
agonist-dependent translocation to the plasma membrane (4, 5).

In addition to this general domain architecture, ongoing research is
unveiling the existence of regions involved in interaction with different
cellular proteins and of regulatory phosphorylation sites in the GRK2

4