Cholecystokinin-B/gastrin receptor signaling pathway involves tyrosine phosphorylations of p125FAK and p42MAP

Oncogene. 1994 Mar;9(3):861-7.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 3T3 Cells / drug effects
  • Animals
  • Cell Adhesion Molecules / metabolism*
  • Cloning, Molecular
  • Focal Adhesion Kinase 1
  • Focal Adhesion Protein-Tyrosine Kinases
  • Gastrins / pharmacology
  • Humans
  • Mice
  • Mitogen-Activated Protein Kinase 1
  • Phosphorylation
  • Protein Serine-Threonine Kinases / metabolism*
  • Protein-Tyrosine Kinases / metabolism*
  • Proto-Oncogene Proteins c-fos / genetics
  • Proto-Oncogene Proteins c-myc / genetics
  • RNA, Messenger / biosynthesis
  • Receptor, Cholecystokinin B
  • Receptors, Cholecystokinin / genetics
  • Receptors, Cholecystokinin / metabolism*
  • Signal Transduction*
  • Sincalide / pharmacology
  • Tyrosine / metabolism*

Substances

  • Cell Adhesion Molecules
  • Gastrins
  • Proto-Oncogene Proteins c-fos
  • Proto-Oncogene Proteins c-myc
  • RNA, Messenger
  • Receptor, Cholecystokinin B
  • Receptors, Cholecystokinin
  • Tyrosine
  • gastrin I
  • Protein-Tyrosine Kinases
  • Focal Adhesion Kinase 1
  • Focal Adhesion Protein-Tyrosine Kinases
  • PTK2 protein, human
  • Ptk2 protein, mouse
  • Protein Serine-Threonine Kinases
  • Mitogen-Activated Protein Kinase 1
  • Sincalide