Document Detail

Possible involvement of normal p21 H-ras in the insulin/insulinlike growth factor 1 signal transduction pathway.
MedLine Citation:
PMID:  2555688     Owner:  NLM     Status:  MEDLINE    
Expression of a mutant H-ras gene confers a transformed phenotype to rat-1 fibroblasts which is basically independent of exogenous growth factors (GFs). Rat-1 cells induced to express high levels of the normal H-ras gene were also found to display a transformed phenotype. In contrast to cells expressing mutant H-ras, these cells were dependent on GFs. We used this difference in GF dependence to analyze a possible involvement of exogenous GFs in H-ras function. Compared with untransformed rat-1 cells, cells overexpressing normal H-ras displayed an elevated response toward insulinlike growth factor 1 (IGF-1), insulin, and bombesin and an increased sensitivity toward phosphatidic acids. It was found that 8-bromo-cyclic AMP inhibited the responses to all GFs in rat-1 cells but had no effect on mutant-H-ras-transformed cells. In cells overexpressing normal H-ras, 8-bromo-cyclic AMP inhibited the responses to all GFs except those to insulin and IGF-1. This implies that overexpression of normal H-ras in the presence of insulin/IGF-1 is functionally similar to the expression of mutant H-ras, since mutant H-ras can circumvent this block by itself. These and other results strongly suggest a functional linkage between insulin/IGF-1 and normal p21 H-ras.
B M Burgering; A J Snijders; J A Maassen; A J van der Eb; J L Bos
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Publication Detail:
Type:  Comparative Study; Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Molecular and cellular biology     Volume:  9     ISSN:  0270-7306     ISO Abbreviation:  Mol. Cell. Biol.     Publication Date:  1989 Oct 
Date Detail:
Created Date:  1989-12-29     Completed Date:  1989-12-29     Revised Date:  2009-11-19    
Medline Journal Info:
Nlm Unique ID:  8109087     Medline TA:  Mol Cell Biol     Country:  UNITED STATES    
Other Details:
Languages:  eng     Pagination:  4312-22     Citation Subset:  IM    
Department of Medical Biochemistry, Sylvius Laboratories, Leiden, The Netherlands.
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MeSH Terms
8-Bromo Cyclic Adenosine Monophosphate / pharmacology
Cell Division / drug effects
Cell Line
Cell Line, Transformed
Cell Transformation, Neoplastic / metabolism
Cyclic AMP / physiology
DNA Replication / drug effects
Gene Expression
Growth Substances / physiology*
Insulin / physiology
Insulin-Like Growth Factor I / physiology
Oncogene Protein p21(ras) / physiology*
Receptor, Insulin / metabolism
Receptors, Cell Surface / metabolism
Receptors, Somatomedin
Signal Transduction / physiology
Reg. No./Substance:
0/Growth Substances; 0/Receptors, Cell Surface; 0/Receptors, Somatomedin; 11061-68-0/Insulin; 23583-48-4/8-Bromo Cyclic Adenosine Monophosphate; 60-92-4/Cyclic AMP; 67763-96-6/Insulin-Like Growth Factor I; EC, Insulin; EC Protein p21(ras)

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