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    Nat Cell Biol. 2011 Jun;13(6):660-7. Epub 2011 May 15.

    Protein kinase A governs a RhoA-RhoGDI protrusion-retraction pacemaker in migrating cells.

    Tkachenko E, Sabouri-Ghomi M, Pertz O, Kim C, Gutierrez E, Machacek M, Groisman A, Danuser G, Ginsberg MH.

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    Department of Medicine, University of California San Diego, 9500 Gilman Drive, Mail Code 0726, La Jolla, California 92093, USA.

    Abstract

    The cyclical protrusion and retraction of the leading edge is a hallmark of many migrating cells involved in processes such as development, inflammation and tumorigenesis. The molecular identity of the signalling mechanisms that control these cycles has remained unknown. Here, we used live-cell imaging of biosensors to monitor spontaneous morphodynamic and signalling activities, and employed correlative image analysis to examine the role of cyclic-AMP-activated protein kinase A (PKA) in protrusion regulation. PKA activity at the leading edge is closely synchronized with rapid protrusion and with the activity of RhoA. Ensuing PKA phosphorylation of RhoA and the resulting increased interaction between RhoA and RhoGDI (Rho GDP-dissociation inhibitor) establish a negative feedback mechanism that controls the cycling of RhoA activity at the leading edge. Thus, cooperation between PKA, RhoA and RhoGDI forms a pacemaker that governs the morphodynamic behaviour of migrating cells.

    PMID:
    21572420
    [PubMed - indexed for MEDLINE]

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