PKCδ Localization at the Membrane Increases Matrix Traction Force Dependent on PLCγ1/EGFR Signaling

• Main Authors: Jamison, Joshua (Author), Wang, James C.-H (Author), Wells, Alan (Author), Lauffenburger, Douglas A. (Contributor)
• Other Authors: Massachusetts Institute of Technology. Department of Biological Engineering (Contributor)
• Format: Article
• Language: English
• Published: Public Library of Science, 2014-01-10T15:52:24Z.
• Subjects: Article
• Online Access: Get fulltext

During wound healing, fibroblasts initially migrate into the wound bed and later contract the matrix. Relevant mediators of transcellular contractility revealed by systems analyses are protein kinase c delta/myosin light chain-2 (PKCδ/MLC-2). PKCδ is activated by growth factor-driven PLCγ1 hydrolysis of phosphoinositide bisphosphate (PIP[subscript 2]) hydrolysis when it becomes tranlocated to the membrane. This leads to MLC-2 phosphorylation that regulates myosin for contractility. Furthermore, PKCδ n-terminus mediates PKCδ localization to the membrane in relative proximity to PLCγ1 activity. However, the role this localization and the relationship to its activation and signaling of force is not well understood. Therefore, we investigated whether the membrane localization of PKCδ mediates the transcellular contractility of fibroblasts.
National Institutes of Health (U.S.) (T32 HL094295)
National Institutes of Health (U.S.) (R01 GM069668)
National Institutes of Health (U.S.) (AR061395)
National Institutes of Health (U.S.) (AR060920)