Myosin light chain kinase A is activated by cGMP-dependent and cGMP-independent pathways.
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.
Boston Biomedical Research Institute, 64 Grove Street, Watertown, MA 02472-2829, USA.
Jonathan M
JM
Goldberg
Eric S
ES
Wolpin
Leonard
L
Bosgraaf
Bryan K
BK
Clarkson
Peter J M
PJ
Van Haastert
Janet L
JL
Smith
D000818:Animals; D002352:Carrier Proteins / Q000737:chemistry / Q000378:metabolism; D002633:Chemotaxis; D003208:Concanavalin A / Q000494:pharmacology; D006152:Cyclic GMP / Q000378:metabolism* / Q000494:pharmacology; D048749:Cytokinesis; D004023:Dictyostelium / Q000166:cytology / Q000187:drug effects / Q000201:enzymology; D004789:Enzyme Activation / Q000187:drug effects; D017353:Gene Deletion; D047908:Intracellular Signaling Peptides and Proteins / Q000737:chemistry / Q000378:metabolism; D008954:Models, Biological; D018994:Myosin Light Chains / Q000378:metabolism; D009219:Myosin-Light-Chain Kinase / Q000378:metabolism*; D010766:Phosphorylation; D015398:Signal Transduction / Q000187:drug effects
D002352:Carrier Proteins; D047908:Intracellular Signaling Peptides and Proteins; D018994:Myosin Light Chains; C022994:cyclic GMP-binding protein; D003208:Concanavalin A; D009219:Myosin-Light-Chain Kinase; D006152:Cyclic GMP