Mouse class III myosins: Kinase activity and phosphorylation sites

Jasbir S. Dalal, Stanley M. Stevens, Sophie Alvarez, Nathalie Munoz, Karen E. Kempler, Andrea C. Dosé, Beth Burnside, Barbara Anne Battelle

Research output: Contribution to journalArticle

6 Scopus citations

Abstract

As class III unconventional myosins are motor proteins with an N-terminal kinase domain, it seems likely they play a role in both signaling and actin based transport. A growing body of evidence indicates that the motor functions of human class IIIA myosin, which has been implicated in progressive hearing loss, are modulated by intermolecular autophosphorylation. However, the phosphorylation sites have not been identified. We studied the kinase activity and phosphorylation sites of mouse class III myosins, mMyo3A and 3B, which are highly similar to their human orthologs. We demonstrate that the kinase domains of mMyo3A and 3B are active kinases, and that they have similar, if not identical, substrate specificities. We show that the kinase domains of these proteins autophosphorylate, and that they can phosphorylate sites within their myosin and tail domains. Using liquid chromatography-mass spectrometry, we identified phosphorylated sites in the kinase, myosin motor and tail domains of both mMyo3A and 3B. Most of the phosphorylated sites we identified and their consensus phosphorylation motifs are highly conserved among vertebrate class III myosins, including human class III myosins. Our findings are a major step toward understanding how the functions of class III myosins are regulated by phosphorylation.

Original languageEnglish (US)
Pages (from-to)772-784
Number of pages13
JournalJournal of Neurochemistry
Volume119
Issue number4
DOIs
Publication statusPublished - Nov 1 2011

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Keywords

  • Ste20 kinase
  • hair cells
  • myosin phosphorylation
  • non-syndromic deafness (DFNB30)
  • photoreceptors
  • unconventional myosin

ASJC Scopus subject areas

  • Biochemistry
  • Cellular and Molecular Neuroscience

Cite this

Dalal, J. S., Stevens, S. M., Alvarez, S., Munoz, N., Kempler, K. E., Dosé, A. C., ... Battelle, B. A. (2011). Mouse class III myosins: Kinase activity and phosphorylation sites. Journal of Neurochemistry, 119(4), 772-784. https://doi.org/10.1111/j.1471-4159.2011.07468.x