Linked Life Data

12483534

Source:http://linkedlifedata.com/resource/pubmed/id/12483534

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
57
pubmed:dateCreated
2002-12-16
pubmed:abstractText
Etk/Bmx, a member of the Tec family of non-receptor tyrosine kinase, is characterized by an N-terminal PH domain and has recently been shown to be involved in the regulation of various cellular processes, including proliferation, differentiation, motility and apoptosis. Since VEGF and the activation of its signaling pathway have been implicated in modulating a variety of biological responses, we characterized the role of Etk-dependent signaling pathways involved in the upregulation of VEGF expression, and explored the functional implications of this enhancement in sustaining cell proliferation and survival. Using Northern and Western analyses, transient transfections, and pharmacological agents, we demonstrate that Etk activation alone is sufficient to transcriptionally induce VEGF expression, independent of the previously identified hypoxia response element (HRE), in both Pa-4 epithelial and TR-BBB endothelial cells under normoxia. In addition, Etk utilizes both MEK/ERK and PI3-K/Pak1 signaling pathways in concert to activate VEGF transcription. Functionally, Etk activation elicits a profound stimulatory effect on TR-BBB cell proliferation and formation of capillary-like networks in Matrigel containing reduced levels of growth factors. Finally, antisense oligonucleotides against either endogenous VEGF or Etk abrogate the proliferation of Etk-activated TR-BBB cells, and exogenous VEGF treatment stimulates endogenous Etk tyrosine phosphorylation in HUVECs. Taken together, these results indicate that VEGF is both an Etk downstream target gene and an Etk upstream activator, constituting a reciprocal Etk-VEGF autoregulatory loop. These findings, to our knowledge, are the first delineation of a network of positive feedforward signaling pathways that converge on the Etk-VEGF axis, causally associating Etk-mediation of VEGF induction with enhanced cellular processes in both epithelial and endothelial cells.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Dec
pubmed:issn
0950-9232
pubmed:author
pubmed:issnType
Print
pubmed:day
12
pubmed:volume
21
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
8817-29
pubmed:dateRevised
2009-11-19
pubmed:meshHeading
pubmed:year
2002
pubmed:articleTitle
Coordinating Etk/Bmx activation and VEGF upregulation to promote cell survival and proliferation.
pubmed:affiliation
Department of Molecular Pharmacology and Toxicology, University of Southern California, Los Angeles, California, CA 90033, USA.
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S.