%0 Journal Article %1 Wittau2000 %A Wittau, N. %A Grosse, R. %A Kalkbrenner, F. %A Gohla, A. %A Schultz, G. %A Gudermann, T. %D 2000 %J Oncogene %K & 1-Methyl-3-isobutylxanthine/pharmacology 1/metabolism 2 3 3T3 AMP/physiology Actins/metabolism Adhesion Animals Bordetella/pharmacology C C/antagonists COS Calcium Carcinoma, Cell Cell/metabolism/*pathology Cells/drug Cultured/metabolism Cyclic Diacylglycerol-Lyase Enzyme Factors, Fusion G12-G13 GTP-Binding Galanin Galanin, Galanin/metabolism/pharmacology Gi-Go/*physiology Gohla Gq-G11 Heterotrimeric Humans Indoles/pharmacology Inhibitors/pharmacology Inositol Intracellular Isoproterenol/pharmacology Kinase Kinases Kinases/metabolism Kinases/physiology Lung Maleimides/pharmacology Mice Microfilaments/metabolism Mitogen-Activated Neoplasm Neoplasms/metabolism/*pathology Neuropeptide/drug Peptides Pertussis Phosphates/metabolism Phosphatidylinositol Phospholipases/metabolism Protein Protein-Serine-Threonine Protein/physiology Proteins Proteins/*physiology Proteins/antagonists Proteins/genetics/physiology Recombinant Signaling Signaling/drug Small Subunits, Toxin Transfection Tumor Type Virulence alpha and effects effects/*physiology inhibitors/*physiology inhibitors/physiology rho-Associated rhoA Receptor %N 37 %P 4199-209 %T The galanin receptor type 2 initiates multiple signaling pathways in small cell lung cancer cells by coupling to G(q), G(i) and G(12) proteins %U http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=10980593 %V 19 %X Neuropeptides like galanin produced and released by small cell lung cancer (SCLC) cells are considered principal mitogens in these tumors. We identified the galanin receptor type 2 (GALR2) as the only galanin receptor expressed in H69 and H510 cells. Photoaffinity labeling of G proteins in H69 cell membranes revealed that GALR2 activates G proteins of three subfamilies: G(q), G(i), and G(12). In H69 cells, galanin-induced Ca2+ mobilization was pertussis toxin-insensitive. While phorbol ester-induced extracellular signal-regulated kinase (ERK) activation required protein kinase C (PKC) activity, preincubation of H69 cells with the PKC-inhibitor GF109203X had no effect on galanin-dependent ERK activity. A rise of the intracellular calcium concentration was necessary and sufficient to mediate galanin-induced ERK activation. In support of G(i) coupling, stimulation of GALR2 expressed in HEK293 cells inhibited isoproterenol-induced cAMP accumulation and raised cAMP levels in COS-7 cells when coexpressed with a chimeric G alpha(S)-G alpha(i) protein In H69 cells, galanin activated the monomeric GTPase RhoA and induced stress fiber formation in Swiss 3T3 cells expressing GALR2. Thus, we provide the first direct evidence that in SCLC the mitogenic neuropeptide galanin, interacting with GALR2, simultaneously activates multiple classes of G proteins and signals through the G(q) phospholipase C/calcium sequence and a G(12)/Rho pathway. Oncogene (2000) 19, 4199 - 4209

@article{Wittau2000, abstract = {Neuropeptides like galanin produced and released by small cell lung cancer (SCLC) cells are considered principal mitogens in these tumors. We identified the galanin receptor type 2 (GALR2) as the only galanin receptor expressed in H69 and H510 cells. Photoaffinity labeling of G proteins in H69 cell membranes revealed that GALR2 activates G proteins of three subfamilies: G(q), G(i), and G(12). In H69 cells, galanin-induced Ca2+ mobilization was pertussis toxin-insensitive. While phorbol ester-induced extracellular signal-regulated kinase (ERK) activation required protein kinase C (PKC) activity, preincubation of H69 cells with the PKC-inhibitor GF109203X had no effect on galanin-dependent ERK activity. A rise of the intracellular calcium concentration was necessary and sufficient to mediate galanin-induced ERK activation. In support of G(i) coupling, stimulation of GALR2 expressed in HEK293 cells inhibited isoproterenol-induced cAMP accumulation and raised cAMP levels in COS-7 cells when coexpressed with a chimeric G alpha(S)-G alpha(i) protein In H69 cells, galanin activated the monomeric GTPase RhoA and induced stress fiber formation in Swiss 3T3 cells expressing GALR2. Thus, we provide the first direct evidence that in SCLC the mitogenic neuropeptide galanin, interacting with GALR2, simultaneously activates multiple classes of G proteins and signals through the G(q) phospholipase C/calcium sequence and a G(12)/Rho pathway. Oncogene (2000) 19, 4199 - 4209}, added-at = {2010-12-14T18:12:02.000+0100}, author = {Wittau, N. and Grosse, R. and Kalkbrenner, F. and Gohla, A. and Schultz, G. and Gudermann, T.}, biburl = {https://www.bibsonomy.org/bibtex/27da198304912ca3a7445a6b7f54ee149/pharmawuerz}, endnotereftype = {Journal Article}, interhash = {8c44e6144e7512f5f63c8f348ef6db92}, intrahash = {7da198304912ca3a7445a6b7f54ee149}, issn = {0950-9232 (Print) 0950-9232 (Linking)}, journal = {Oncogene}, keywords = {& 1-Methyl-3-isobutylxanthine/pharmacology 1/metabolism 2 3 3T3 AMP/physiology Actins/metabolism Adhesion Animals Bordetella/pharmacology C C/antagonists COS Calcium Carcinoma, Cell Cell/metabolism/*pathology Cells/drug Cultured/metabolism Cyclic Diacylglycerol-Lyase Enzyme Factors, Fusion G12-G13 GTP-Binding Galanin Galanin, Galanin/metabolism/pharmacology Gi-Go/*physiology Gohla Gq-G11 Heterotrimeric Humans Indoles/pharmacology Inhibitors/pharmacology Inositol Intracellular Isoproterenol/pharmacology Kinase Kinases Kinases/metabolism Kinases/physiology Lung Maleimides/pharmacology Mice Microfilaments/metabolism Mitogen-Activated Neoplasm Neoplasms/metabolism/*pathology Neuropeptide/drug Peptides Pertussis Phosphates/metabolism Phosphatidylinositol Phospholipases/metabolism Protein Protein-Serine-Threonine Protein/physiology Proteins Proteins/*physiology Proteins/antagonists Proteins/genetics/physiology Recombinant Signaling Signaling/drug Small Subunits, Toxin Transfection Tumor Type Virulence alpha and effects effects/*physiology inhibitors/*physiology inhibitors/physiology rho-Associated rhoA Receptor}, month = {Aug 31}, note = {Wittau, N Grosse, R Kalkbrenner, F Gohla, A Schultz, G Gudermann, T England Oncogene Oncogene. 2000 Aug 31;19(37):4199-209.}, number = 37, pages = {4199-209}, shorttitle = {The galanin receptor type 2 initiates multiple signaling pathways in small cell lung cancer cells by coupling to G(q), G(i) and G(12) proteins}, timestamp = {2010-12-14T18:20:51.000+0100}, title = {The galanin receptor type 2 initiates multiple signaling pathways in small cell lung cancer cells by coupling to G(q), G(i) and G(12) proteins}, url = {http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=10980593}, volume = 19, year = 2000 }