Molecular cloning and characterization of a novel regulator of G-protein signaling from mouse hematopoietic stem cells

A novel regulator of G-protein signaling (RGS) has been isolated from a hig hly purified population of mouse long-term hematopoietic stem cells, and de signated RGS18. It has 234 amino acids consisting of a central RGS box and short divergent NH2 and COOH termini, The calculated molecular weight of RG S18 is 27,610 and the isoelectric point is 8.63. Mouse RGS18 is expressed f rom a single gene and shows tissue specific distribution. It is most highly expressed in bone marrow followed by fetal liver, spleen, and then lung. I n bone marrow, RGS18 level is highest in long-term and short-term hematopoi etic stem cells, and is decreased as they differentiate into more committed multiple progenitors. The human RGS18 ortholog has a tissue-specific expre ssion pattern similar to that of mouse RGS18. Purified RGS18 interacts with the alpha subunit of both G(i) and G(q) subfamilies. The results of in vit ro GTPase single-turnover assays using G alpha (i) indicated that RGS18 acc elerates the intrinsic GTPase activity of G alpha (i). Transient overexpres sion of RGS18 attenuated inositol phosphates production via angiotensin rec eptor and transcriptional activation through cAMP-responsive element via M1 muscarinic receptor. This suggests RGS18 can act on G(q)-mediated signalin g pathways in vivo.