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 Citations (Scopus)

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 2007
Externally publishedYes

Fingerprint

Receptor, Fibroblast Growth Factor, Type 1
Fibroblast Growth Factor Receptors
Pancreas
JNK Mitogen-Activated Protein Kinases
p38 Mitogen-Activated Protein Kinases
Fibroblast Growth Factor 1
Fibroblast Growth Factors
Fibroblast Growth Factor 2
Mitogen-Activated Protein Kinases
Pancreatic Neoplasms
Cell Movement
In Situ Hybridization
Tyrosine
Phosphorylation
Pharmacology
Messenger RNA
Proteins

Keywords

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

ASJC Scopus subject areas

  • Gastroenterology
  • Endocrinology

Cite this

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

In: Pancreas, Vol. 35, No. 2, 08.2007, p. 147-157.

Research output: Contribution to journalArticle

Liu, Zhanbing ; Ishiwata, Toshiyuki ; Zhou, Shaxia ; Maier, Susanne ; Henne-Bruns, Doris ; Korc, Murray ; Bachem, Max ; Kornmann, Marko. / 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. In: Pancreas. 2007 ; Vol. 35, No. 2. pp. 147-157.
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T1 - 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

AU - Liu, Zhanbing

AU - Ishiwata, Toshiyuki

AU - Zhou, Shaxia

AU - Maier, Susanne

AU - Henne-Bruns, Doris

AU - Korc, Murray

AU - Bachem, Max

AU - Kornmann, Marko

PY - 2007/8

Y1 - 2007/8

N2 - 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.

AB - 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.

KW - Fibroblast growth factor

KW - Mitogen-activated protein kinase

KW - Pancreas

KW - Signaling cascades

KW - Tyrosine kinase receptor

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