title: RGS19 enhances cell proliferation through its C-terminal PDZ motif.
abstract: Regulator of G protein signaling 19 (RGS19), also known as Galpha-interacting protein (GAIP), is a GTPase activating protein (GAP) for Galpha(i) subunits. Apart from its GAP function, RGS19 has been implicated in growth factor signaling through binding to GAIP-interacting protein C-terminus (GIPC) via its C-terminal PDZ-binding motif. To gain additional insight on its function, we have stably expressed RGS19 in a number of mammalian cell lines and examined its effect on cell proliferation. Interestingly, overexpression of RGS19 stimulated the growth of HEK293, PC12, Caco2, and NIH3T3 cells. This growth promoting effect was not shared by other RGS proteins including RGS4, RGS10 and RGS20. Despite its ability to stimulate cell proliferation, RGS19 failed to induce neoplastic transformation in NIH3T3 cells as determined by focus formation and soft-agar assays, and it did not induce tumor growth in athymic nude mice. Deletion mutants of RGS19 lacking the PDZ-binding motif failed to complex with GIPC and did not exhibit any growth promoting effect. Overexpression of GIPC alone in HEK293 cells stimulated cell proliferation whereas its knockdown in H1299 non-small cell lung carcinomas suppressed cell proliferation. This study demonstrates that RGS19, in addition to acting as a GAP, is able to stimulate cell proliferation in a GIPC-dependent manner.
authors.affiliation: Department of Biochemistry, The Biotechnology Research Institute, and The Molecular Neuroscience Center, Hong Kong University of Science and Technology, Clear Water Bay, Kowloon, Hong Kong.
authors.forename: Prudence H
authors.initials: PH
authors.lastname: Tso
authors.forename: Yingchun
authors.initials: Y
authors.lastname: Wang
authors.forename: Sivia Y S
authors.initials: SY
authors.lastname: Wong
authors.forename: Lydia S W
authors.initials: LS
authors.lastname: Poon
authors.forename: Anthony S L
authors.initials: AS
authors.lastname: Chan
authors.forename: Yung H
authors.initials: YH
authors.lastname: Wong
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000378:metabolism; D020816:Amino Acid Motifs; D000818:Animals; D002352:Carrier Proteins / Q000378:metabolism; D002460:Cell Line; D049109:Cell Proliferation; D006801:Humans; D051379:Mice; D008819:Mice, Nude; D009479:Neuropeptides / Q000378:metabolism; D010766:Phosphorylation; D011485:Protein Binding; D020710:RGS Proteins / Q000032:analysis / Q000737:chemistry / Q000378:metabolism*; D034622:RNA Interference; D034741:RNA, Small Interfering / Q000378:metabolism; D051381:Rats; D014162:Transfection
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D002352:Carrier Proteins; C492009:GIPC1 protein, human; C115271:Gipc1 protein, mouse; D009479:Neuropeptides; D020710:RGS Proteins; D034741:RNA, Small Interfering; C097187:regulator of G-protein signalling 19