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 tyrosine1173 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 tyrosine1173 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 tyrosine1173, whereas both EGFR tyrosine kinase and EGFR autophosphorylation at Y1173 play a critical role in EGF-induced AP-1 activation.
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Abbreviations
- AP-1:
-
activator protein-1
- ERKs:
-
extracellular signal-regulated protein kinases
- MAPKs:
-
mitogen-activated protein kinases
- JNKs:
-
c-Jun N-terminal kinases
- TPA:
-
12-O-tetradecanoylphorbol-13-acetate
- EGF:
-
epidermal growth factor
- FBS:
-
fet al bovine serum
- MEM:
-
minimal essential medium
References
Baker VL, Murai JT and Taylor RN . (1998). Placenta, 19, 475–482.
Blumberg PM . (1991). Mol. Carcinog., 4, 339–344.
Carpenter G . (1999). J. Cell. Biol., 1146, 697–702.
Chen WS, Lazar CS, Poenie M, Tsien RY, Gill GN and Rosenfeld MG . (1987). Nature, 328, 820–823.
Chen N, Ma WY, She QB, Wu E, Liu G, Bode AM and Dong Z . (2001). J. Biol. Chem., 276, 46 722–46 728.
Ciardiello F . (2000). Drugs, 60(Suppl. 1): 25–32; Discussion 41–42.
Gulliford T, Ouyang X and Epstein RJ . (1999). Cell Signal., 11, 245–252.
Gschwind A, Zwick E, Prenzel N, Leserer M and Ullrich A . (2001). Oncogene, 20, 1594–1600.
Hackel PO, Zwick E, Prenzel N and Ullrich A . (1999). Curr. Opin. Cell. Biol., 11, 184–189.
Huang C, Ma W, Bowden GT and Dong Z . (1996a). J. Biol. Chem., 271, 31262–31268.
Huang C, Ma W-Y and Dong Z . (1996b). Mol. Cell. Biol., 16, 6427–6435.
Huang C, Ma W-Y, Dawson MI, Rincon M, Flavell RA and Dong Z . (1997a). Proc. Natl. Acad. Sci. USA, 94, 5826–5830.
Huang C, Ma W-Y, Hanenberger D, Cleary MP, Bowden GT and Dong Z . (1997b). J. Biol. Chem., 272, 26325–26331.
Huang C, Ma W and Dong Z . (1997c). Oncogene, 14, 1945–1954.
Huang C, Schmid PC, Ma WY, Schmid HH and Dong Z . (1997d). J. Biol. Chem., 272, 4187–4194.
Huang C, Ma W-Y, Hecht SS, Dong Z . (1997e). Cancer Res., 57, 2873–2878.
Huang C, Ma W-Y, Young MR, Colburn N and Dong Z . (1998). Proc. Natl. Acad. Sci. USA, 95, 156–161.
Huang C, Ma WY and Dong Z . (1999a). Oncogene, 18, 2828–2835.
Huang C, Li J, Ma W-Y and Dong, Z . (1999b). J. Biol. Chem., 274, 29672–29676.
Jochum W, Passegue E and Wagner EF . (2001). Oncogene, 20, 2401–2412.
Kong AN, Yu R, Hebbar V, Chen C, Owuor E, Hu R, Ee R and Mandlekar S . (2001). Mutat Res., 4804–81, 231–241.
Lin CR, Chen WS, Lazar CS, Carpenter CD, Gill GN, Evans RM and Rosenfeld MG . (1986). Cell, 44, 839–848.
Mendelsohn J and Baselga J . (2000). Oncogene, 19, 6550–6565.
Moghal N and Sternberg PW . (1999). Curr. Opin. Cell. Biol., 11, 190–196.
Prenzel N, Zwick E, Daub H, Leserer M, Abraham R, Wallasch C and Ullrich A . (1999). Nature, 402, 884–888.
Prywes R, Livneh E, Ullrich A and Schlessinger J . (1986). EMBO J., 5, 2179–2190.
Schaap D, van der Wal J, Howe LR, Marshall CJ and van Blitterswijk WJ . (1993). J. Biol. Chem., 268, 20 232–20 236.
Schlessinger J . (2000). Cell, 103, 211–225.
Schwartz MA and Baron V . (1999). Curr. Opin. Cell. Biol., 11, 197–202.
Shaulian E and Karin M . (2001). Oncogene, 20, 2390–2400.
Simon MA . (2000). Cell, 103, 13–15.
Slaga TJ, Fischer SM, Weeks CE, Klein-Szanto AJ and Reiners J . (1982). J. Cell. Biochem., 18, 99–119.
Troppmair J, Bruder JT, Munoz H, Lloyd PA, Kyriakis J, Banerjee P, Avruch J and Rapp UR . (1994). J. Biol. Chem., 269, 7030–7035.
Watts RG, Huang C, Young MR, Li JJ, Dong Z, Pennie WD and Colburn NH . (1998). Oncogene, 17, 3493–3498.
Wells A . (1999). Int. J. Biochem. Cell. Biol., 31, 637–643.
Xian W, Kiguchi K, Imamoto A, Rupp T, Zilberstein A and DiGiovanni J . (1995). Cell Growth Differ., 6, 1447–1455.
Yarden Y . (2001). Eur. J. Cancer, 37 (Suppl 4), S3–S8.
Young MR, Li JJ, Rincon M, Flavell RA, Sathyanarayana BK, Hunziker R and Colburn N . (1999). Proc. Natl. Acad. Sci. USA, 96, 9827–9832.
Acknowledgements
This work was supported in part by NIH grant numbers ES 00260 and CA 16087.
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Li, J., Ma, C., Huang, Y. et al. Differential requirement of EGF receptor and its tyrosine kinase for AP-1 transactivation induced by EGF and TPA. Oncogene 22, 211–219 (2003). https://doi.org/10.1038/sj.onc.1206102
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DOI: https://doi.org/10.1038/sj.onc.1206102
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