Regulation of kinesin activity by phosphorylation of kinesin-associated proteins

• Published in: The Journal of biological chemistry 1994-07, Vol.269 (29), p.19176-19182
• Main Authors: J M McIlvain, Jr, J K Burkhardt, S Hamm-Alvarez, Y Argon, M P Sheetz
• Format: Article
• Language: English
• Subjects: Animals; Biological and medical sciences; Cell Movement; Cell structures and functions; Cytoplasmic Granules - physiology; Cytoskeleton, cytoplasm. Intracellular movements; Ethers, Cyclic - pharmacology; Fundamental and applied biological sciences. Psychology; In Vitro Techniques; Kinesin - metabolism; Macromolecular Substances; Mice; Microtubules - metabolism; Molecular and cellular biology; Molecular Weight; Okadaic Acid; Phosphoproteins - metabolism; Phosphorylation; T-Lymphocytes, Cytotoxic - ultrastructure
• ISSN: 0021-9258; 1083-351X
• DOI: 10.1016/s0021-9258(17)32291-3

The mechanochemical motor proteins of the kinesin and cytoplasmic dynein families play important roles in microtubule-based intracellular motility. Although movement and distribution of organelles like secretory granules, vesicles, endoplasmic reticulum, and chromosomes depend on the activity of these motor proteins, little is known about the regulation of this movement. We report here that the hyperphosphorylation of components of the kinesin complex by treatment with okadaic acid increases kinesin motor activity at least 2-fold. The stimulation was observed using both a granule motility assay and a microtubule gliding assay, indicating that phosphorylation enhances the activity of the motor itself, rather than the affinity of the motor for membrane organelles. Under stimulatory conditions, three proteins that co-purify with kinesin (with mobilities of 150, 79, and 73 kDa) are consistently hyperphosphorylated. Dephosphorylation of these proteins reduces kinesin activity to basal levels. Therefore, we conclude that kinesin motor activity is directly modulated by the phosphorylation state of kinesin-associated proteins.