Human gastrin-releasing peptide receptor mediates sustained CREB phosphorylation and transactivation in HuTu 80 duodenal cancer cells

FEBS Lett. 2002 Sep 11;527(1-3):109-13. doi: 10.1016/s0014-5793(02)03177-0.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Bombesin / pharmacology
  • Calcium / metabolism
  • Cyclic AMP Response Element-Binding Protein / drug effects
  • Cyclic AMP Response Element-Binding Protein / genetics
  • Cyclic AMP Response Element-Binding Protein / metabolism*
  • Cyclic AMP-Dependent Protein Kinases / metabolism
  • Duodenal Neoplasms / metabolism*
  • Enzyme Inhibitors / pharmacology
  • Humans
  • Imidazoles / pharmacology
  • Mitogen-Activated Protein Kinase 1 / metabolism
  • Mitogen-Activated Protein Kinase 3
  • Mitogen-Activated Protein Kinases / antagonists & inhibitors
  • Mitogen-Activated Protein Kinases / metabolism
  • Phosphorylation / drug effects
  • Protein Kinase C / metabolism
  • Pyridines / pharmacology
  • Receptors, Bombesin / metabolism*
  • Recombinant Fusion Proteins / drug effects
  • Recombinant Fusion Proteins / genetics
  • Recombinant Fusion Proteins / metabolism
  • Serine / metabolism
  • Transcription, Genetic
  • Transcriptional Activation*
  • Tumor Cells, Cultured
  • p38 Mitogen-Activated Protein Kinases

Substances

  • Cyclic AMP Response Element-Binding Protein
  • Enzyme Inhibitors
  • Imidazoles
  • Pyridines
  • Receptors, Bombesin
  • Recombinant Fusion Proteins
  • Serine
  • Cyclic AMP-Dependent Protein Kinases
  • Protein Kinase C
  • Mitogen-Activated Protein Kinase 1
  • Mitogen-Activated Protein Kinase 3
  • Mitogen-Activated Protein Kinases
  • p38 Mitogen-Activated Protein Kinases
  • SB 203580
  • Bombesin
  • Calcium