PMID- 15271882
OWN - NLM
STAT- MEDLINE
DCOM- 20041130
LR  - 20211203
IS  - 0013-7227 (Print)
IS  - 0013-7227 (Linking)
VI  - 145
IP  - 11
DP  - 2004 Nov
TI  - Evidence that basal activity, but not transactivation, of the epidermal growth 
      factor receptor tyrosine kinase is required for insulin-like growth factor 
      I-induced activation of extracellular signal-regulated kinase in oral carcinoma 
      cells.
PG  - 4976-84
AB  - IGF-I receptor (IGF-IR) is involved in numerous biological functions via its 
      major downstream signaling molecules, extracellular signal-regulated kinase (ERK) 
      and phosphatidylinositol 3'-kinase/Akt. The IGF-I-induced activation of ERK, but 
      not that of Akt, is reportedly mediated by the transactivation of the epidermal 
      growth factor receptor (EGFR) tyrosine kinase (TK). The mechanism for the 
      EGFR-TK-dependent activation, however, still remains largely unknown. We found 
      that an oral carcinoma cell line overexpressing EGFR, Ca9-22, exhibited 
      IGF-I-induced activation of both Akt and ERK, but that only the latter was 
      significantly decreased by a specific inhibitor of EGFR-TK, tyrphostin AG1478. In 
      this report we provide evidence for the existence in this cell line of a novel 
      mechanism by which IGF-I induces ERK activation in a manner that is dependent on 
      the basal level of EGFR-TK activity, but is independent of receptor 
      transactivation. In addition, we show that c-Raf kinase is likely to be a key 
      regulator of this mechanism. The elucidation of such a unique mechanism involving 
      cross-talk between EGFR and heterologous receptors may shed additional light on 
      the clinical use of EGFR-TK inhibitors in antitumor therapies.
FAU - Kuribayashi, Ami
AU  - Kuribayashi A
AD  - Molecular Diagnosis and Therapeutics, Department of Oral Restitution, Graduate 
      School, Tokyo Medical and Dental University, 1-5-45 Yushima, Bunkyo-ku, Tokyo 
      113-8549, Japan.
FAU - Kataoka, Keiko
AU  - Kataoka K
FAU - Kurabayashi, Tohru
AU  - Kurabayashi T
FAU - Miura, Masahiko
AU  - Miura M
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20040722
PL  - United States
TA  - Endocrinology
JT  - Endocrinology
JID - 0375040
RN  - 0 (Adaptor Proteins, Signal Transducing)
RN  - 0 (Enzyme Inhibitors)
RN  - 0 (GRB2 Adaptor Protein)
RN  - 0 (GRB2 protein, human)
RN  - 0 (HBEGF protein, human)
RN  - 0 (Heparin-binding EGF-like Growth Factor)
RN  - 0 (Intercellular Signaling Peptides and Proteins)
RN  - 0 (Proto-Oncogene Proteins)
RN  - 0 (Quinazolines)
RN  - 0 (SHC1 protein, human)
RN  - 0 (Shc Signaling Adaptor Proteins)
RN  - 0 (Src Homology 2 Domain-Containing, Transforming Protein 1)
RN  - 0 (Tyrphostins)
RN  - 170449-18-0 (RTKI cpd)
RN  - 62229-50-9 (Epidermal Growth Factor)
RN  - 67763-96-6 (Insulin-Like Growth Factor I)
RN  - EC 2.7.10.1 (ErbB Receptors)
RN  - EC 2.7.10.1 (Receptor, IGF Type 1)
RN  - EC 2.7.11.1 (AKT1 protein, human)
RN  - EC 2.7.11.1 (Protein Serine-Threonine Kinases)
RN  - EC 2.7.11.1 (Proto-Oncogene Proteins c-akt)
RN  - EC 2.7.11.1 (Proto-Oncogene Proteins c-raf)
RN  - EC 2.7.11.24 (Mitogen-Activated Protein Kinases)
RN  - EC 3.6.5.2 (ras Proteins)
SB  - IM
MH  - Adaptor Proteins, Signal Transducing/metabolism
MH  - Cell Line, Tumor
MH  - Enzyme Inhibitors/pharmacology
MH  - Epidermal Growth Factor/metabolism/pharmacology
MH  - ErbB Receptors/*metabolism
MH  - GRB2 Adaptor Protein
MH  - Heparin-binding EGF-like Growth Factor
MH  - Humans
MH  - Insulin-Like Growth Factor I/*pharmacology
MH  - Intercellular Signaling Peptides and Proteins
MH  - Mitogen-Activated Protein Kinases/metabolism
MH  - *Mouth Neoplasms
MH  - Phosphorylation/drug effects
MH  - Protein Serine-Threonine Kinases/metabolism
MH  - Proto-Oncogene Proteins/metabolism
MH  - Proto-Oncogene Proteins c-akt
MH  - Proto-Oncogene Proteins c-raf/metabolism
MH  - Quinazolines
MH  - Receptor Cross-Talk/physiology
MH  - Receptor, IGF Type 1/metabolism
MH  - Shc Signaling Adaptor Proteins
MH  - Signal Transduction/drug effects/*physiology
MH  - Src Homology 2 Domain-Containing, Transforming Protein 1
MH  - Tyrphostins/antagonists & inhibitors/pharmacology
MH  - ras Proteins/metabolism
EDAT- 2004/07/24 05:00
MHDA- 2004/12/16 09:00
CRDT- 2004/07/24 05:00
PHST- 2004/07/24 05:00 [pubmed]
PHST- 2004/12/16 09:00 [medline]
PHST- 2004/07/24 05:00 [entrez]
AID - en.2004-0713 [pii]
AID - 10.1210/en.2004-0713 [doi]
PST - ppublish
SO  - Endocrinology. 2004 Nov;145(11):4976-84. doi: 10.1210/en.2004-0713. Epub 2004 Jul 
      22.