Human fibroblast growth factor receptor 1-IIIb is a functional fibroblast growth factor receptor expressed in the pancreas and involved in proliferation and movement of pancreatic ductal cells

Zhanbing Liu, Toshiyuki Ishiwata, Shaxia Zhou, Susanne Maier, Doris Henne-Bruns, Murray Korc, Max Bachem, Marko Kornmann

Research output: Contribution to journalArticle

7 Scopus citations

Abstract

OBJECTIVES: The possible functions of the human IIIb-messenger RNA splice variant of fibroblast growth factor (FGF) receptor 1 (FGFR-1 IIIb) are yet to be delineated. In this study, the expression and functionality of the human FGFR-1 IIIb were characterized in the pancreas. METHODS: In situ hybridization with a specific FGFR-1 IIIb probe in human pancreatic tissues demonstrated that FGFR-1 IIIb localized in normal pancreatic acinar and in ductallike pancreatic cancer cells. To further assess the potential role of this receptor, a full-length human FGFR-1 IIIb was stably expressed in TAKA-1 pancreatic ductal cells not expressing endogenous FGFR-1. RESULTS: The FGFR-1 IIIb-expressing TAKA-1 cells synthesized a glycosylated 110-kd protein capable of inducing proliferation on incubation with exogenous FGF-1, -2, and -4. These effects were paralleled by tyrosine phosphorylation of FGFR substrate 2 and association of FGFR substrate 2 with FGFR-1 IIIb. The FGF-1, -2, and -10 induced the activation of p44/42 mitogen-activated protein kinase (MAPK), p38 MAPK, and c-Jun N-terminal kinase. Pharmacological inhibition revealed that FGF-induced proliferation was dependent on the concomitant activation of p44/42 MAPK and c-Jun N-terminal kinase. The FGFR-1 IIIb expression enhanced single-cell movement and plating efficacy. CONCLUSIONS: Our results demonstrate that the human FGFR-1 IIIb variant is a functional FGFR expressed in the pancreas that can alter pancreatic functions that regulate proliferation, adhesion, and movement.

Original languageEnglish (US)
Pages (from-to)147-157
Number of pages11
JournalPancreas
Volume35
Issue number2
DOIs
StatePublished - Aug 1 2007

Keywords

  • Fibroblast growth factor
  • Mitogen-activated protein kinase
  • Pancreas
  • Signaling cascades
  • Tyrosine kinase receptor

ASJC Scopus subject areas

  • Internal Medicine
  • Endocrinology, Diabetes and Metabolism
  • Hepatology
  • Endocrinology

Fingerprint Dive into the research topics of 'Human fibroblast growth factor receptor 1-IIIb is a functional fibroblast growth factor receptor expressed in the pancreas and involved in proliferation and movement of pancreatic ductal cells'. Together they form a unique fingerprint.

  • Cite this