A tandem repeat of a fragment of Listeria monocytogenes internalin B protein induces cell survival and proliferation
| العنوان: | A tandem repeat of a fragment of Listeria monocytogenes internalin B protein induces cell survival and proliferation |
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| المؤلفون: | Donald P. Bottaro, Ana P. Marquez, Ognoon Mungunsukh, Young H. Lee, Fabiola Cecchi, Regina M. Day |
| المصدر: | American Journal of Physiology-Lung Cellular and Molecular Physiology. 299:L905-L914 |
| بيانات النشر: | American Physiological Society, 2010. |
| سنة النشر: | 2010 |
| مصطلحات موضوعية: | STAT3 Transcription Factor, Pulmonary and Respiratory Medicine, Cell Survival, Physiology, Biology, Rats, Sprague-Dawley, Bacterial Proteins, Cell Movement, Physiology (medical), medicine, Animals, Internalin, Extracellular Signal-Regulated MAP Kinases, Protein kinase B, Tissue homeostasis, Cell Proliferation, Repetitive Sequences, Nucleic Acid, Hepatocyte Growth Factor, Cell growth, Endothelial Cells, Membrane Proteins, Articles, Cell Biology, Proto-Oncogene Proteins c-met, Molecular biology, Angiotensin II, Rats, Enzyme Activation, Cattle, Female, Hepatocyte growth factor, Signal transduction, Proto-Oncogene Proteins c-akt, Signal Transduction, medicine.drug |
| الوصف: | 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 (InlB36–321) was demonstrated to bind to and partially activate the HGF receptor Met. InlB36–321has a stable β-sheet structure and is easily produced in its native conformation by Escherichia coli . We cloned InlB36–321(1×InlB36–321) and engineered a head-to-tail repeat of InlB36–321with a linker peptide (2×InlB36–321); 1×InlB36–321and 2×InlB36–321were purified from E. coli . Both 1× and 2×InlB36–321activated the Met tyrosine kinase. We subsequently compared signal transduction of the two proteins in primary lung endothelial cells. 2×InlB36–321activated ERK1/2, STAT3, and phosphatidylinositol 3-kinase/Akt pathways, whereas 1×InlB36–321activated only STAT3 and ERK1/2. The 2×InlB36–321promoted improved motility compared with 1×InlB36–321and additionally stimulated proliferation equivalent to full-length HGF. Both the 1× and 2×InlB36–321prevented 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×InlB36–321to mimic HGF make it a potential candidate as a pharmaceutical agent for tissue repair. |
| تدمد: | 1522-1504 1040-0605 |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::1b9382d0e04c1c1aab99b8948a07098fTest https://doi.org/10.1152/ajplung.00094.2010Test |
| حقوق: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....1b9382d0e04c1c1aab99b8948a07098f |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 15221504 10400605 |
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