Differential requirement of EGF receptor and its tyrosine kinase for AP-1 transactivation induced by EGF and TPA

Jingxia Li; Cuiling Ma; Yi Huang; Jia Luo; Chuanshu Huang

doi:10.1038/sj.onc.1206102

Back

Differential requirement of EGF receptor and its tyrosine kinase for AP-1 transactivation induced by EGF and TPA

Journal article

Peer reviewed

Differential requirement of EGF receptor and its tyrosine kinase for AP-1 transactivation induced by EGF and TPA

Jingxia Li, Cuiling Ma, Yi Huang, Jia Luo and Chuanshu Huang

Oncogene, Vol.22(2), pp.211-219

01/16/2003

DOI: 10.1038/sj.onc.1206102

PMID: 12527890

View Online

Abstract

The transcription factor activator protein-1 (AP-1) has been implicated in a large variety of biological processes including cell differentiation, proliferation, apoptosis and oncogenic transformation. It is thought that the 12-O-tetradecanoylphorbol-13-acetate (TPA)-induced AP-1 activity is because of the activation of the PKC/MAPK/AP-1 pathway, although the detailed molecular mechanism has not been fully characterized. The tyrosine kinases of epidermal growth factor receptor (EGFR) lie at the head of a complex of signal transduction cascade that modulates cell proliferation, survival, adhesion, migration and differentiation. Currently, little is known about whether EGFR or its tyrosine kinase is necessary for TPA-induced AP-1 activation. In the present study, we investigated this issue using a well-characterized mouse fibroblast B82 cell line, which is devoid of the EGFR, and its stable transfectants with either wild-type EGFR (B82L) or tyrosine kinase-deficient EGFR (mutation at Lys-721) (B82M721). We demonstrated that the TPA or epidermal growth factor (EGF) induced AP-1 activation in the B82L cells that express wild-type EGFR, but not in the B82 cell, whereas autophosphorylation at tyrosine(1173) of EGFR in B82L cells was only induced by EGF, but not TPA. The expression of tyrosine kinase-deficient EGFR (mutation at Lys-721) (B82M721) resulted in deficiency of AP-1 induction in cellular response to EGF, while TPA treatment led to fully AP-1 activation. Furthermore, the mutation at Lys-721 of EGFR resulted in impairing of EGFR autophosphorylation at tyrosine(1173) induced by EGF. Based on these results, we conclude that TPA-induced AP-1 activation requires the basal level-EGFR protein, but not EGFR tyrosine kinase and EGFR autophosphorylation at tyrosine(1173), whereas both EGFR tyrosine kinase and EGFR autophosphorylation at Y(1173) play a critical role in EGF-induced AP-1 activation.

Animals

Cells, Cultured

Enzyme Activation - drug effects

Epidermal Growth Factor - metabolism

Epidermal Growth Factor - pharmacology

Fibroblasts

Humans

Lysine - genetics

Mice

Mitogen-Activated Protein Kinases - drug effects

Mitogen-Activated Protein Kinases - metabolism

Phosphorylation

Point Mutation

Receptor, Epidermal Growth Factor - genetics

Receptor, Epidermal Growth Factor - metabolism

Tetradecanoylphorbol Acetate - pharmacology

Transcription Factor AP-1 - drug effects

Transcription Factor AP-1 - genetics

Transcription Factor AP-1 - metabolism

Transcriptional Activation - drug effects

Transfection

Tyrosine - metabolism

Details

Title: Subtitle: Differential requirement of EGF receptor and its tyrosine kinase for AP-1 transactivation induced by EGF and TPA
Creators: Jingxia Li - New York University
Cuiling Ma - West Virginia University
Yi Huang - West Virginia University
Jia Luo - West Virginia University
Chuanshu Huang - New York University
Resource Type: Journal article
Publication Details: Oncogene, Vol.22(2), pp.211-219
DOI: 10.1038/sj.onc.1206102
PMID: 12527890
NLM abbreviation: Oncogene
ISSN: 0950-9232
eISSN: 1476-5594
Grant note: CA 16087 / NCI NIH HHS ES 00260 / NIEHS NIH HHS
Language: English
Date published: 01/16/2003
Academic Unit: Pathology
Record Identifier: 9984201119802771

Metrics

12 Record Views

37 Times Cited - Web of Science