G protein-coupled receptor kinase 2 (GRK2) is a ubiquitous, essential protein 
kinase that is emerging as an integrative node in many signaling networks. 
Moreover, changes in GRK2 abundance and activity have been identified in several 
inflammatory, cardiovascular disease, and tumor contexts, suggesting that those 
alterations may contribute to the initiation or development of pathologies. GRKs 
were initially identified as key players in the desensitization and 
internalization of multiple G protein-coupled receptors (GPCRs), but GRK2 also 
phosphorylates several non-GPCR substrates and dynamically associates with a 
variety of proteins related to signal transduction. Ongoing research in our 
laboratory is aimed at understanding how specific GRK2 interactomes are 
orchestrated in a stimulus-, context-, or cell type-specific manner. We have 
recently identified an interaction between GRK2 and histone deacetylase 6 
(HDAC6) that modulates cell spreading and motility. HDAC6 is a major cytoplasmic 
a-tubulin deacetylase that is involved in cell motility and adhesion. GRK2 
dynamically and directly associates with and phosphorylates HDAC6 to stimulate 
its a-tubulin deacetylase activity at specific cellular localizations, such as 
the leading edge of migrating cells, thus promoting local tubulin deacetylation 
and enhanced motility. GRK2-HDAC6-mediated regulation of tubulin acetylation 
also modulates cellular spreading. This GRK2-HDAC6 functional interaction may 
have important implications in pathological contexts related to epithelial cell 
migration.