Characterization of the Zebrafish Homolog of Zipper Interacting Protein Kinase
- Carr, B.W., Basepayne, T.L., Chen, L., Jayashankar, V., Weiser, D.C.
- International Journal of Molecular Sciences 15: 11597-11613 (Journal)
- Registered Authors
- Weiser, Douglas C.
- ZIPK, DAPK3, Mypt1, MLC2, Zebrafish, Actomyosin, Stress fiber, Zebrafish, Danio rerio
- MeSH Terms
- Actin Cytoskeleton/metabolism
- Active Transport, Cell Nucleus
- Amino Acid Sequence
- Cell Nucleus/metabolism*
- Death-Associated Protein Kinases/chemistry
- Death-Associated Protein Kinases/genetics
- Death-Associated Protein Kinases/metabolism*
- HEK293 Cells
- HeLa Cells
- Molecular Sequence Data
- Species Specificity
- 24983477 Full text @ Int. J. Mol. Sci.
Carr, B.W., Basepayne, T.L., Chen, L., Jayashankar, V., Weiser, D.C. (2014) Characterization of the Zebrafish Homolog of Zipper Interacting Protein Kinase. International Journal of Molecular Sciences. 15:11597-11613.
Zipper-interacting protein kinase (ZIPK) is a conserved vertebrate-specific regulator of actomyosin contractility in smooth muscle and non-muscle cells. Murine ZIPK has undergone an unusual divergence in sequence and regulation compared to other ZIPK orthologs. In humans, subcellular localization is controlled by phosphorylation of threonines 299 and 300. In contrast, ZIPK subcellular localization in mouse and rat is controlled by interaction with PAR-4. We carried out a comparative biochemical characterization of the regulation of the zebrafish ortholog of ZIPK. Like the human orthologs zebrafish ZIPK undergoes nucleocytoplasmic-shuttling and is abundant in the cytoplasm, unlike the primarily nuclear rat ZIPK. Rat ZIPK, but not human or zebrafish ZIPK, interacts with zebrafish PAR-4. Mutation of the conserved residues required for activation of the mammalian orthologs abrogated activity of the zebrafish ZIPK. In contrast to the human ortholog, mutation of threonine 299 and 300 in the zebrafish ZIPK has no effect on the activity or subcellular localization. Thus, we found that zebrafish ZIPK functions in a manner most similar to the human ZIPK and quite distinct from murine orthologs, yet the regulation of subcellular localization is not conserved.
Genes / Markers
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Engineered Foreign Genes