Document Detail


Epidermal growth factor-dependent dissociation of CrkII proto-oncogene product from the epidermal growth factor receptor in human glioma cells.
MedLine Citation:
PMID:  10595738     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Human glioma cells frequently overexpress epidermal growth factor receptor (EGFR). We found that the CrkII proto-oncogene product was associated with the EGFR in human glioma cells in the absence of epidermal growth factor (EGF). EGF stimulation of glioma cells induced the phosphorylation of tyrosine 221 of the CrkII protein, which correlates with its dissociation from the EGFR. By contrast, Shc and Grb2 were inducibly associated with the EGFR in response to EGF stimulation of glioma cells. In A431 cells, epidermoid carcinoma cells which overexpress EGFR, CrkII was tyrosine-phosphorylated and associated with the EGFR in an EGF-dependent manner. Therefore, the dissociation of CrkII from the EGFR upon stimulation with EGF appears to be specific to glioma cells. The Cbl oncogene product was also tyrosine-phosphorylated in U87MG glioma cells upon EGF stimulation. However, unlike in other cell lines, CrkII was not inducibly bound to Cbl in U87MG glioma cells. Thus, EGF-dependent binding of CrkII to phosphotyrosine-containing proteins appears to be suppressed in glioma cells. To evaluate the physiological role of dissociation of CrkII from EGFR, we expressed the CrkII-23 mutant in glioma cells. CrkII-23 mutant, which was isolated as a suppressor gene of the EGF-dependent transformation of NRK cells, binds constitutively to EGFR. We found that expression of CrkII-23 inhibited the anchorage-independent growth of the glioma cells in the presence of EGF. Taken together, these data implicate EGF-dependent dissociation of CrkII from EGFR in the oncogenicity of human glioma cells.
Authors:
H Katayama; Y Hashimoto; E Kiyokawa; M Nakaya; A Sakamoto; R Machinami; T Kurata; N Mochizuki; M Matsuda
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Publication Detail:
Type:  Journal Article    
Journal Detail:
Title:  Japanese journal of cancer research : Gann     Volume:  90     ISSN:  0910-5050     ISO Abbreviation:  Jpn. J. Cancer Res.     Publication Date:  1999 Oct 
Date Detail:
Created Date:  2000-01-04     Completed Date:  2000-01-04     Revised Date:  2009-11-19    
Medline Journal Info:
Nlm Unique ID:  8509412     Medline TA:  Jpn J Cancer Res     Country:  JAPAN    
Other Details:
Languages:  eng     Pagination:  1096-103     Citation Subset:  IM    
Affiliation:
Department of Pathology, National Institute of Infectious Diseases, Tokyo.
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MeSH Terms
Descriptor/Qualifier:
Cell Adhesion
Cell Division
Epidermal Growth Factor / pharmacology*
Gene Expression Regulation, Neoplastic
Glioma
Humans
Kinetics
Phosphorylation
Phosphotyrosine / metabolism
Protein Binding
Protein Kinases / genetics,  metabolism*
Proto-Oncogene Proteins*
Proto-Oncogene Proteins c-crk
Proto-Oncogenes*
Receptor, Epidermal Growth Factor / drug effects,  metabolism*
Tumor Cells, Cultured
src Homology Domains
Chemical
Reg. No./Substance:
0/Proto-Oncogene Proteins; 0/Proto-Oncogene Proteins c-crk; 21820-51-9/Phosphotyrosine; 62229-50-9/Epidermal Growth Factor; EC 2.7.-/Protein Kinases; EC 2.7.10.1/Receptor, Epidermal Growth Factor

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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