Myosin light chain kinase A is activated by cGMP-dependent and cGMP-independent pathways

Goldberg, Jonathan M.; Wolpin, Eric S.; Bosgraaf, Leonard; Clarkson, Bryan K.; Van Haastert, Peter J.M.; Smith, Janet L.

doi:10.1016/j.febslet.2006.03.008

« Previous Next »FEBS Letters
Volume 580, Issue 8 , Pages 2059-2064, 3 April 2006

Myosin light chain kinase A is activated by cGMP-dependent and cGMP-independent pathways

Edited by Michael R. Bubb

Jonathan M. Goldberg
- Boston Biomedical Research Institute, 64 Grove Street, Watertown, MA 02472-2829, United States
Eric S. Wolpin
- Boston Biomedical Research Institute, 64 Grove Street, Watertown, MA 02472-2829, United States
Leonard Bosgraaf
- Department of Biochemistry, University of Groningen, Nijenborgh 4, 9747 AG Groningen, The Netherlands
Bryan K. Clarkson
- Boston Biomedical Research Institute, 64 Grove Street, Watertown, MA 02472-2829, United States
Peter J.M. Van Haastert
- Department of Biochemistry, University of Groningen, Nijenborgh 4, 9747 AG Groningen, The Netherlands
Janet L. Smith
- Boston Biomedical Research Institute, 64 Grove Street, Watertown, MA 02472-2829, United States
- Corresponding author. Fax: +1 617 972 1761.

Received 7 November 2005; received in revised form 13 February 2006; accepted 1 March 2006. published online 10 March 2006.

Abstract

Stimulation of Dictyostelium cells with the chemoattractant cAMP results in transient phosphorylation of the myosin regulatory light chain (RLC). We show that myosin light chain kinase A (MLCK-A) is responsible for RLC phosphorylation during chemotaxis, and that MLCK-A itself is transiently phosphorylated on threonine-166, dramatically increasing its catalytic activity. MLCK-A activation during chemotaxis is highly responsive to cellular cGMP levels and the cGMP-binding protein GbpC. MLCK-A⁻ cells have a partial cytokinesis defect, and do not phosphorylate RLC in response to concanavalin A (conA), but cells lacking cGMP or GbpC divide normally and phosphorylate in response to conA. Thus MLCK-A is activated by a cGMP/GbpC-independent mechanism activated during cytokinesis or by conA, and a cGMP/GbpC-dependent pathway during chemotaxis.

Keywords: Dictyostelium, Chemotaxis, cGMP, Myosin, Regulatory light chain, Phosphorylation