Cholecystokinin-B/gastrin receptor signaling pathway involves tyrosine phosphorylations of p125FAK and p42MAP.
The neuro-intestinal peptide hormone cholecystokinin (CCK)/gastrin has been suggested to have a trophic effect on gastro-intestinal tract in vivo as well as in vitro. In the present study, the human CCK-B/gastrin receptor was expressed in mouse NIH3T3 fibroblasts to investigate the molecular basis of signal transduction pathway of the guanine nucleotide regulatory protein (G protein)-coupled receptor. Human CCK-B/gastrin receptor expressed in NIH3T3 cells coupled efficiently to phosphoinositide hydrolysis and mobilization of intracellular Ca2+, and transduced mitogenic signals assessed by [3H]thymidine incorporation in a dose-dependent manner. Moreover, CCK-8 or gastrin I alone promoted the cell growth in serum-free medium. CCK-8 induced tyrosine phosphorylation of several protein species. Among them, mitogen-activated protein (MAP) kinase was tyrosine phosphorylated and activated in response to CCK-8, as was induced by platelet-derived growth factor (PDGF). In contrast, tyrosine phosphorylation of p125FAK (focal adhesion kinase) was induced by CCK-8 but not by PDGF. CCK-8 as well as gastrin I induced the expression of early responsive genes such as c-fos and c-myc. These results suggest that CCK-B/gastrin receptors might transmit mitogenic signals by cross-talking with the tyrosine kinase cascades.
Taniguchi
T
T
Department of Medicine, Kobe University School of Medicine, Japan.
Matsui
T
T
Ito
M
M
Murayama
T
T
Tsukamoto
T
T
Katakami
Y
Y
Chiba
T
T
Chihara
K
K
D016475:3T3 Cells / Q000187:drug effects; D000818:Animals; D015815:Cell Adhesion Molecules / Q000378:metabolism*; D003001:Cloning, Molecular; D051417:Focal Adhesion Kinase 1; D051416:Focal Adhesion Protein-Tyrosine Kinases; D005755:Gastrins / Q000494:pharmacology; D006801:Humans; D051379:Mice; D019950:Mitogen-Activated Protein Kinase 1; D010766:Phosphorylation; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism*; D011505:Protein-Tyrosine Kinases / Q000378:metabolism*; D016760:Proto-Oncogene Proteins c-fos / Q000235:genetics; D016271:Proto-Oncogene Proteins c-myc / Q000235:genetics; D012333:RNA, Messenger / Q000096:biosynthesis; D043887:Receptor, Cholecystokinin B; D011949:Receptors, Cholecystokinin / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction; D012844:Sincalide / Q000494:pharmacology; D014443:Tyrosine / Q000378:metabolism*
D015815:Cell Adhesion Molecules; D005755:Gastrins; D016760:Proto-Oncogene Proteins c-fos; D016271:Proto-Oncogene Proteins c-myc; D012333:RNA, Messenger; D043887:Receptor, Cholecystokinin B; D011949:Receptors, Cholecystokinin; D014443:Tyrosine; C036227:gastrin I; D011505:Protein-Tyrosine Kinases; D051417:Focal Adhesion Kinase 1; D051416:Focal Adhesion Protein-Tyrosine Kinases; C496050:PTK2 protein, human; C496051:Ptk2 protein, mouse; D017346:Protein Serine-Threonine Kinases; D019950:Mitogen-Activated Protein Kinase 1; D012844:Sincalide