Linked Life Data

20889677

Source:http://linkedlifedata.com/resource/pubmed/id/20889677

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
6
pubmed:dateCreated
2010-12-6
pubmed:abstractText
Hepatocyte growth factor (HGF) is critical for tissue homeostasis and repair in many organs including the lung, heart, kidney, liver, nervous system, and skin. HGF is a heterodimeric protein containing 20 disulfide bonds distributed among an amino-terminal hairpin, four kringle domains, and a serine protease-like domain. Due to its complex structure, recombinant production of HGF in prokaryotes requires denaturation and refolding, processes that are impractical for large-scale manufacture. Thus, pharmaceutical quantities of HGF are not available despite its potential applications. A fragment of the Listeria monocytogenes internalin B protein from amino acids 36-321 (InlB??????) was demonstrated to bind to and partially activate the HGF receptor Met. InlB?????? has a stable ?-sheet structure and is easily produced in its native conformation by Escherichia coli. We cloned InlB?????? (1×InlB??????) and engineered a head-to-tail repeat of InlB?????? with a linker peptide (2×InlB??????); 1×InlB?????? and 2×InlB?????? were purified from E. coli. Both 1× and 2×InlB?????? activated the Met tyrosine kinase. We subsequently compared signal transduction of the two proteins in primary lung endothelial cells. 2×InlB?????? activated ERK1/2, STAT3, and phosphatidylinositol 3-kinase/Akt pathways, whereas 1×InlB?????? activated only STAT3 and ERK1/2. The 2×InlB?????? promoted improved motility compared with 1×InlB?????? and additionally stimulated proliferation equivalent to full-length HGF. Both the 1× and 2×InlB?????? prevented apoptosis by the profibrotic peptide angiotensin II in cell culture and ex vivo lung slice cultures. The ease of large-scale production and capacity of 2×InlB?????? to mimic HGF make it a potential candidate as a pharmaceutical agent for tissue repair.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Dec
pubmed:issn
1522-1504
pubmed:author
pubmed:issnType
Electronic
pubmed:volume
299
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
L905-14
pubmed:dateRevised
2011-2-15
pubmed:meshHeading
pubmed-meshheading:20889677-Animals, pubmed-meshheading:20889677-Bacterial Proteins, pubmed-meshheading:20889677-Cattle, pubmed-meshheading:20889677-Cell Movement, pubmed-meshheading:20889677-Cell Proliferation, pubmed-meshheading:20889677-Cell Survival, pubmed-meshheading:20889677-Endothelial Cells, pubmed-meshheading:20889677-Enzyme Activation, pubmed-meshheading:20889677-Extracellular Signal-Regulated MAP Kinases, pubmed-meshheading:20889677-Female, pubmed-meshheading:20889677-Hepatocyte Growth Factor, pubmed-meshheading:20889677-Membrane Proteins, pubmed-meshheading:20889677-Proto-Oncogene Proteins c-akt, pubmed-meshheading:20889677-Proto-Oncogene Proteins c-met, pubmed-meshheading:20889677-Rats, pubmed-meshheading:20889677-Rats, Sprague-Dawley, pubmed-meshheading:20889677-Repetitive Sequences, Nucleic Acid, pubmed-meshheading:20889677-STAT3 Transcription Factor, pubmed-meshheading:20889677-Signal Transduction
pubmed:year
2010
pubmed:articleTitle
A tandem repeat of a fragment of Listeria monocytogenes internalin B protein induces cell survival and proliferation.
pubmed:affiliation
Dept. of Pharmacology, Uniformed Services University of the Health Sciences, Center for Cancer Research, National Cancer Institute, Bethesda, Maryland, USA. rday@usuhs.mil
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't, Research Support, N.I.H., Extramural, Research Support, N.I.H., Intramural