RGS14, a GTPase-activating protein for Gialpha, attenuates Gialpha- and G13alpha-mediated signaling pathways.
Regulator of G protein signaling (RGS) proteins are a family of approximately 20 proteins that negatively regulate signaling through heterotrimeric G protein-coupled receptors. The RGS proteins act as GTPase-activating proteins (GAPs) for certain Galpha subunits and as effector antagonists for Gqalpha. Mouse RGS14 encodes a 547-amino-acid protein with an N-terminal RGS domain, which is highly expressed in lymphoid tissues. In this study, we demonstrate that RGS14 is a GAP for Gialpha subfamily members and it attenuates interleukin-8 receptor-mediated mitogen-activated protein kinase activation. However, RGS14 does not exhibit GAP activity toward Gsalpha or Gqalpha nor does it regulate Gsalpha- or Gqalpha-mediated signaling pathways. Although RGS14 does not act as a GAP for G12/13alpha, it impairs c-fos serum response element activation induced by either a constitutively active mutant of G13alpha (G13alphaQ226L) or by carbachol stimulation of muscarinic type 1 receptors. An RGS14 mutant (EN92/93AA), which does not block Gialpha-linked signaling, also inhibits serum response element activation. RGS14 localizes predominantly in the cytosol, but it can be recruited to membranes by expression of G13alphaQ226L. Although RGS14 is constitutively expressed in lymphoid cells, agents that activate B or T lymphocytes further enhance its levels. Taken together, our results suggest that signals generated after lymphocyte activation may via RGS14 directly impinge on Gialpha- or G13alpha-mediated cellular processes in lymphocytes, such as adhesion and migration.
Cho
H
H
B-Cell Molecular Immunology Section, Laboratory of Immunoregulation, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland 20892-1876, USA.
Kozasa
T
T
Takekoshi
K
K
De Gunzburg
J
J
Kehrl
J H
JH
D000818:Animals; D001402:B-Lymphocytes / Q000378:metabolism; D019556:COS Cells; D002462:Cell Membrane / Q000378:metabolism; D002478:Cells, Cultured; D003593:Cytoplasm / Q000378:metabolism; D019206:GTP-Binding Protein alpha Subunits, Gi-Go / Q000378:metabolism*; D020690:GTPase-Activating Proteins / Q000378:metabolism*; D015870:Gene Expression; D006801:Humans; D048052:Mitogen-Activated Protein Kinase 3; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D020710:RGS Proteins / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction; D013347:Subcellular Fractions; D013601:T-Lymphocytes / Q000378:metabolism
D020690:GTPase-Activating Proteins; D020710:RGS Proteins; C491400:RGS14 protein, human; C491399:Rgs14 protein, mouse; D048052:Mitogen-Activated Protein Kinase 3; D020928:Mitogen-Activated Protein Kinases; D019206:GTP-Binding Protein alpha Subunits, Gi-Go