Differentially regulated expression of the G-protein-coupled receptor kinases, beta ARK and GRK6, during myelomonocytic cell development in vitro

G-protein-coupled receptor kinases (GRKs) mediate agonist-specific phosphorylation and desensitization of G-protein-coupled receptors. Previous studies have shown that several of these kinases are expressed in hematopoietic cells and that GRK expression is modulated during T-lymphocyte activation. Here, we analyzed the regulation of beta-adrenergic receptor kinase (beta ARK) and GRK6 expression and activity in myelomonocytic and lymphoid cells. In the promyelocytic cell line HL-60, GRK6 protein levels and activity rose twofold to fourfold over the course of treatment with agents that induce differentiation toward either the myeloid (dimethyl sulfoxide and retinoic acid) or monocytic [1 alpha,25(OH)(2)-vitamin D-3] lineage, whereas beta ARK protein levels and activity were only slightly altered, In contrast, treatment with phorbol 12,13-myristic acetate (PMA) led to a reduction in steady-state levels and activity-of both beta ARK and GRK6. Treatment of human lymphocytes with several polyclonal activators (phytohemagglutinin, anti-CD3 antibody and interleukin-2) resulted in enhanced beta ARK and GRK6 mRNA and protein levels and increased activity of both kinases. In contrast, PMA and calcium ionophore treatment significantly elevated GRK6 protein levels, while decreasing beta ARK expression. These data demonstrate that beta ARK and GRK6 expression are differentially regulated during myelomonocytic cell development and lymphocyte activation. (C) 1996 by The American Society of Hematology.