Human gastrin-releasing peptide receptor mediates sustained CREB phosphorylation and transactivation in HuTu 80 duodenal cancer cells.
The G protein-coupled human gastrin-releasing peptide receptor (hGRP-R) is frequently found aberrantly expressed in human cancers of the colon, stomach, and lung, and its ligand-specific activation has been implicated in cell proliferation and differentiation. Here, we demonstrated hGRP-R activation stimulated sustained cyclic AMP response element binding protein (CREB) phosphorylation and transactivation in duodenal cancer cells through a protein kinase C and partially p38 mitogen-activated protein kinase-dependent pathway. In contrast, intracellular calcium, ERK1/2, protein kinase A, and PI3 kinase were not involved. This novel signaling mechanism might be of importance for regulation of CREB-dependent gene expression in human cancer expressing functional hGRP-R.
Qu
Xiangping
X
Boston University School of Medicine, Section of Gastroenterology, 650 Albany Street, EBRC, Room 515, Boston, MA 02118, USA.
Xiao
Dongmei
D
Weber
H Christian
HC
D001839:Bombesin / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism; D017362:Cyclic AMP Response Element-Binding Protein / Q000187:drug effects / Q000235:genetics / Q000378:metabolism*; D017868:Cyclic AMP-Dependent Protein Kinases / Q000378:metabolism; D004379:Duodenal Neoplasms / Q000378:metabolism*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006801:Humans; D007093:Imidazoles / Q000494:pharmacology; D019950:Mitogen-Activated Protein Kinase 1 / Q000378:metabolism; D048052:Mitogen-Activated Protein Kinase 3; D020928:Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism; D010766:Phosphorylation / Q000187:drug effects; D011493:Protein Kinase C / Q000378:metabolism; D011725:Pyridines / Q000494:pharmacology; D018004:Receptors, Bombesin / Q000378:metabolism*; D011993:Recombinant Fusion Proteins / Q000187:drug effects / Q000235:genetics / Q000378:metabolism; D012694:Serine / Q000378:metabolism; D014158:Transcription, Genetic; D015533:Transcriptional Activation; D014407:Tumor Cells, Cultured; D048051:p38 Mitogen-Activated Protein Kinases
D017362:Cyclic AMP Response Element-Binding Protein; D004791:Enzyme Inhibitors; D007093:Imidazoles; D011725:Pyridines; D018004:Receptors, Bombesin; D011993:Recombinant Fusion Proteins; D012694:Serine; D017868:Cyclic AMP-Dependent Protein Kinases; D011493:Protein Kinase C; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3; D020928:Mitogen-Activated Protein Kinases; D048051:p38 Mitogen-Activated Protein Kinases; C093642:SB 203580; D001839:Bombesin; D002118:Calcium