Rac regulates phosphorylation of the myosin-II heavy chain, actinomyosin disassembly and cell spreading

• Published in: Nature cell biology Vol. 1; no. 4; pp. 242 - 248
• Main Authors: Collard, John G, van Leeuwen, Frank N, van Delft, Sanne, Kain, Hendrie E, van der Kammen, Rob A
• Format: Journal Article
• Language: English
• Published: England 01.08.1999
• Subjects: Actomyosin - metabolism; Animals; Bradykinin - pharmacology; Calcium - metabolism; Cell Line; Cell Size - physiology; Mice; Myosin Heavy Chains - metabolism; PC12 Cells; Phosphorylation; Protein-Serine-Threonine Kinases - metabolism; rac GTP-Binding Proteins - metabolism; Rac protein; Rats; rho GTP-Binding Proteins - metabolism; Signal Transduction
• ISSN: 1465-7392; 1476-4679; 1476-4679
• DOI: 10.1038/12068

GTPases of the Rho family regulate actinomyosin-based contraction in non-muscle cells. Activation of Rho increases contractility, leading to cell rounding and neurite retraction in neuronal cell lines. Activation of Rac promotes cell spreading and interferes with Rho-mediated cell rounding. Here we show that activation of Rac may antagonize Rho by regulating phosphorylation of the myosin-II heavy chain. Stimulation of PC12 cells or N1E-115 neuroblastoma cells with bradykinin induces phosphorylation of threonine residues in the myosin-II heavy chain; this phosphorylation is Ca2+ dependent and regulated by Rac. Both bradykinin-mediated and constitutive activation of Rac promote cell spreading, accompanied by a loss of cortical myosin II. Our results identify the myosin-II heavy chain as a new target of Rac-regulated kinase pathways, and implicate Rac as a Rho antagonist during myosin-II-dependent cell-shape changes.