Document Detail


Synergistic stimulation of DNA synthesis by bradykinin and vasopressin in Swiss 3T3 cells.
MedLine Citation:
PMID:  8077288     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Vasopressin and bradykinin bind to receptors coupled to GTP-binding proteins and rapidly induce polyphosphoinositide breakdown leading to Ca2+ mobilization and activation of protein kinase C. Both peptides are known to induce mitogenesis in the presence of growth factors that act through receptors with intrinsic tyrosine kinase activity. Surprisingly, addition of a combination of vasopressin and bradykinin to Swiss 3T3 cells synergistically stimulates DNA synthesis in the absence of any other growth factors. This effect is induced at nanomolar concentrations of the peptides and could be inhibited by addition of specific receptor antagonists or broad spectrum neuropeptide antagonists. Bradykinin, which stimulates transient activation of protein kinase C, induces DNA synthesis in synergy with substances that cause long-term activation of protein kinase C, like vasopressin or phorbol 12,13-dibutyrate. Down-regulation of protein kinase C inhibited the induction of mitogenesis by the combination of vasopressin and bradykinin, thus demonstrating the importance of long-term activation of this enzyme for DNA synthesis. Analysis of tyrosine phosphorylated proteins of M(r) = 110,000-130,000 and M(r) = 70,000-80,000 revealed a biphasic response after stimulation with bradykinin, whereas the response induced by vasopressin declined after the initial maximum. The combination of bradykinin with vasopressin caused an enhanced and prolonged increase in tyrosine phosphorylation of these proteins as compared with the individual peptides. Inhibition of tyrosine phosphorylation by tyrphostin was paralleled by inhibition of DNA synthesis. Together, these results demonstrate synergistic stimulation of DNA synthesis by bradykinin and vasopressin via prolonged stimulation of multiple signaling pathways and imply that the interactive effects of Ca(2+)-mobilizing peptides on mitogenesis may be more general than previously thought.
Authors:
K Kiehne; E Rozengurt
Related Documents :
3459728 - Phorbol ester binding and activation of protein kinase c on triton x-100 mixed micelles...
21857648 - Lpa-producing enzyme pa-pla₁α regulates hair follicle development by modulating egfr si...
6233978 - Activation of protein kinase c by non-phorbol tumor promoter, mezerein.
8130278 - Effect of fatty acids and their acyl-coa esters on protein kinase c activity in fibrobl...
17709198 - Neuron-specific phosphorylation of c-jun n-terminal kinase increased in the brain of hy...
9380028 - Menadione cytotoxicity to hep g2 cells and protection by activation of nuclear factor-k...
Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Journal of cellular physiology     Volume:  160     ISSN:  0021-9541     ISO Abbreviation:  J. Cell. Physiol.     Publication Date:  1994 Sep 
Date Detail:
Created Date:  1994-10-05     Completed Date:  1994-10-05     Revised Date:  2006-11-15    
Medline Journal Info:
Nlm Unique ID:  0050222     Medline TA:  J Cell Physiol     Country:  UNITED STATES    
Other Details:
Languages:  eng     Pagination:  502-10     Citation Subset:  IM    
Affiliation:
Imperial Cancer Research Fund, London, United Kingdom.
Export Citation:
APA/MLA Format     Download EndNote     Download BibTex
MeSH Terms
Descriptor/Qualifier:
3T3 Cells
Animals
Bradykinin / pharmacology*
DNA / biosynthesis*
Drug Combinations
Drug Synergism
Intracellular Membranes / physiology
Mice
Mitogens / pharmacology
Signal Transduction / drug effects
Vasopressins / pharmacology*
Chemical
Reg. No./Substance:
0/Drug Combinations; 0/Mitogens; 11000-17-2/Vasopressins; 58-82-2/Bradykinin; 9007-49-2/DNA

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


Previous Document:  Effect of tyrosine kinase inhibition on basal and epidermal growth factor-stimulated human Caco-2 en...
Next Document:  cDNA from human ocular ciliary epithelium homologous to beta ig-h3 is preferentially expressed as an...