1. Essential role for the SLK protein kinase in embryogenesis and placental tissue development.
- Author
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Al-Zahrani KN, Sekhon P, Tessier DR, Yockell-Lelievre J, Pryce BR, Baron KD, Howe GA, Sriram RK, Daniel K, Mckay M, Lo V, Quizi J, Addison CL, Gruslin A, and Sabourin LA
- Subjects
- Animals, Embryo, Mammalian cytology, Female, Mice, Mice, Transgenic, Placenta cytology, Pregnancy, Pregnancy Proteins genetics, Protein Serine-Threonine Kinases genetics, Embryo, Mammalian enzymology, Embryonic Development physiology, Placenta enzymology, Pregnancy Proteins metabolism, Protein Serine-Threonine Kinases metabolism
- Abstract
Background: Over the past decade, the Ste20-like kinase SLK, has been implicated in several signaling processes. SLK repression has been shown to impair cell cycle kinetics and inhibit FAK-mediated cell migration. Here, using a gene trapped allele, we have generated mice expressing a truncated form of the SLK kinase., Results: Our results show that an SLK-LacZ fusion protein is expressed in embryonic stem cells and in embryos throughout development. We find that the SLK-LacZ fusion protein is less efficient at phosphorylating substrates resulting in reduced cell proliferation within the embryos and angiogenic defects in the placentae of the homozygous mutant animals at embryonic day (E) 12.5. This results in marked developmental defects and apoptotic lesions in the embryos by E14.5., Conclusions: Homozygotes expressing the SLK-LacZ fusion protein present with an embryonic lethal phenotype occurring between E12.5 and E14.5. Overall, we demonstrate a requirement for SLK kinase activity in the developing embryo and placenta., (Copyright © 2013 Wiley Periodicals, Inc.)
- Published
- 2014
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