Increased protein phosphorylation of cytoplasmic dynein results in impaired motor function.
Inhibition of serine/threonine protein phosphatases in rat hepatocytes by okadaic acid and microcystin increased the phosphorylation of several components of the cytoplasmic dynein complex. UV light/vanadate cleavage and Western blot analysis revealed that two of these components with molecular masses of approx. 400 kDa and 74 kDa were dynein heavy- and intermediate-chains respectively. This increased phosphorylation resulted in inhibition of dynein ATPase activity, and reduced motor-dependent avidity of endosomal/lysosomal membranes for microtubules.
Runnegar
M T
MT
Department of Medicine, University of Southern California, 1985 Zonal Avenue, Los Angeles, CA 90089-9121, USA.
Wei
X
X
Hamm-Alvarez
S F
SF
D000818:Animals; D001665:Binding Sites; D002478:Cells, Cultured; D003593:Cytoplasm / Q000187:drug effects / Q000378:metabolism; D004398:Dyneins / Q000378:metabolism*; D011992:Endosomes / Q000187:drug effects / Q000378:metabolism; D007425:Intracellular Membranes / Q000187:drug effects / Q000378:metabolism; D016547:Kinesins / Q000378:metabolism; D008099:Liver / Q000166:cytology / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism; D008247:Lysosomes / Q000187:drug effects / Q000378:metabolism; D008297:Male; D052998:Microcystins; D008870:Microtubules / Q000187:drug effects / Q000378:metabolism; D020409:Molecular Motor Proteins / Q000187:drug effects / Q000378:metabolism*; D019319:Okadaic Acid / Q000494:pharmacology; D010456:Peptides, Cyclic / Q000494:pharmacology; D010749:Phosphoprotein Phosphatases / Q000037:antagonists & inhibitors / Q000378:metabolism; D010766:Phosphorylation / Q000187:drug effects; D017346:Protein Serine-Threonine Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley
D052998:Microcystins; D020409:Molecular Motor Proteins; D010456:Peptides, Cyclic; D019319:Okadaic Acid; C078588:microcystin; D017346:Protein Serine-Threonine Kinases; D010749:Phosphoprotein Phosphatases; D004398:Dyneins; D016547:Kinesins