Document Detail

Neurite outgrowth stimulated by the tyrosine kinase inhibitor herbimycin A requires activation of tyrosine kinases and protein kinase C.
MedLine Citation:
PMID:  7514647     Owner:  NLM     Status:  MEDLINE    
Activation of tyrosine kinases is established as an important mechanism for controlling growth cone motility and neurite outgrowth. We have tested the effects of a range of tyrosine kinase inhibitors on neurite outgrowth from postnatal day 4 cerebellar granule cells cultured over confluent monolayers of 3T3 fibroblasts. The only agent that had any effect was herbimycin A, which stimulated neurite outgrowth. The response is shown to be attributable to a direct effect of this tyrosine kinase inhibitor on neurones. The neurite outgrowth response to herbimycin A was inhibited by two other tyrosine kinase inhibitors, which on their own did not affect neurite outgrowth. The data suggest that the response to herbimycin A reflects either a direct or indirect activation of one or more protein tyrosine kinases. Independent signalling events down-stream from tyrosine kinase activation underlying the neurite outgrowth response to herbimycin A include increased activity of protein kinase C and calcium influx into neurones through both N- and L-type calcium channels.
P Doherty; J Furness; E J Williams; F S Walsh
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Journal of neurochemistry     Volume:  62     ISSN:  0022-3042     ISO Abbreviation:  J. Neurochem.     Publication Date:  1994 Jun 
Date Detail:
Created Date:  1994-06-21     Completed Date:  1994-06-21     Revised Date:  2009-11-19    
Medline Journal Info:
Nlm Unique ID:  2985190R     Medline TA:  J Neurochem     Country:  UNITED STATES    
Other Details:
Languages:  eng     Pagination:  2124-31     Citation Subset:  IM    
Department of Experimental Pathology, UMDS, Guy's Hospital, London, England.
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MeSH Terms
Calcium / metabolism
Cerebellum / cytology
Enzyme Activation
Lactams, Macrocyclic
Nerve Tissue Proteins / metabolism
Neurites / drug effects,  physiology*
Neurons / metabolism,  physiology
Phenols / pharmacology
Protein Kinase C / metabolism*
Protein-Tyrosine Kinases / antagonists & inhibitors*,  metabolism*
Quinones / pharmacology*
Tyrosine / analogs & derivatives,  pharmacology
Grant Support
//Wellcome Trust
Reg. No./Substance:
0/Benzoquinones; 0/Lactams, Macrocyclic; 0/Nerve Tissue Proteins; 0/Phenols; 0/Quinones; 125697-92-9/lavendustin A; 21820-51-9/Phosphotyrosine; 55520-40-6/Tyrosine; 70563-58-5/herbimycin; 7440-70-2/Calcium; EC Kinases; EC Kinase C

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