ArticleMolecular biology of the cell2008
Src-mediated cortactin phosphorylation regulates actin localization and injurious blebbing in acinar cells.
Article in Molecular biology of the cell, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers.
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Who cites it
25 citing papers in PubMed.
- Acute lipotoxicity regulates severity of biliary acute pancreatitis without affecting its initiation.The American journal of pathology · 2014Trial
- Elucidation of roles of serine/threonine phosphatases PP1 and PP2A in mediating CCK-stimulated growth and enzyme secretion in pancreatic acinar cells.American journal of physiology. Gastrointestinal and liver physiology · 2025Article
- Visceral fat lipolysis by pancreatic lipases worsens heart failure.Cell reports. Medicine · 2025Article
- A safe method for rapid therapeutic pancreatic cooling.iScience · 2024Article
- Discoveries of GPR39 as an evolutionarily conserved receptor for bile acids and of its involvement in biliary acute pancreatitis.Science advances · 2024Article
- Evidence showing lipotoxicity worsens outcomes in covid-19 patients and insights about the underlying mechanisms.iScience · 2022Article
- Mortality From Coronavirus Disease 2019 Increases With Unsaturated Fat and May Be Reduced by Early Calcium and Albumin Supplementation.Gastroenterology · 2020Article
- Thermodynamic interference with bile acid demicelleization reduces systemic entry and injury during cholestasis.Scientific reports · 2020Article
- Carboxyl Ester Lipase May Not Mediate Lipotoxic Injury during Severe Acute Pancreatitis.The American journal of pathology · 2019Article
- Multimodal Transgastric Local Pancreatic Hypothermia Reduces Severity of Acute Pancreatitis in Rats and Increases Survival.Gastroenterology · 2019Article
- c-Src regulates cargo transit via the Golgi in pancreatic acinar cells.Scientific reports · 2018Article
- Src kinases play a novel dual role in acute pancreatitis affecting severity but no role in stimulated enzyme secretion.American journal of physiology. Gastrointestinal and liver physiology · 2016Article
- Involvement of Membrane Blebbing in Immunological Disorders and Cancer.Medical principles and practice : international journal of the Kuwait University, Health Science Centre · 2016Review
- Article
- Characterization and Predictive Value of Near Infrared 2-Deoxyglucose Optical Imaging in Severe Acute Pancreatitis.PloS one · 2016Article
- Src kinases regulate de novo actin polymerization during exocytosis in neuroendocrine chromaffin cells.PloS one · 2014Article
- Cyclin G2 promotes hypoxia-driven local invasion of glioblastoma by orchestrating cytoskeletal dynamics.Neoplasia (New York, N.Y.) · 2013Article
- Src Dependent Pancreatic Acinar Injury Can Be Initiated Independent of an Increase in Cytosolic Calcium.PloS one · 2013Article
- ADP-ribosylation factor 1 protein regulates trypsinogen activation via organellar trafficking of procathepsin B protein and autophagic maturation in acute pancreatitis.The Journal of biological chemistry · 2012Article
- Ryanodine receptors contribute to bile acid-induced pathological calcium signaling and pancreatitis in mice.American journal of physiology. Gastrointestinal and liver physiology · 2012Article
Corrections and comments
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Authors and funding
2 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Suprastimulation of pancreatic acini is a well-known model for pancreatitis, and it is characterized by actin reorganization and cell blebbing. Currently, however, the mechanisms underlying regulation of these aberrant cytoskeletal and membrane dynamics and how they contribute to cell injury are unclear. We observed that suprastimulation results in a rapid activation of Src and relocalization of the actin-binding protein cortactin from the apical to the basolateral domain at the necks of membrane blebs. Furthermore, Src-mediated cortactin tyrosine phosphorylation was markedly increased after suprastimulation. Pretreatment of acini with Src inhibitors or expression of a cortactin tyrosine phospho-inhibitory mutant reduced actin redistribution and bleb formation induced by suprastimulation in vitro. Importantly, inhibition of Src activity in rat models of suprastimulation-induced pancreatitis substantially reduced disease severity, as indicated by a reduction in serum amylase and pancreatic edema and a striking improvement in tissue histology. These findings indicate a novel, disease-relevant role for Src-mediated cortactin phosphorylation in aberrant reorganization of the actin cytoskeleton, a mechanism that is likely to have implications in other types of cell injury. In addition, they suggest a potential use for Src inhibitors as an approach to reduce cell injury.
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