Expression of a kinase inactive SLK is embryonic lethal and impairs cell migration in fibroblasts

• Published in: Biochimica et biophysica acta. Molecular cell research Vol. 1871; no. 7; p. 119783
• Main Authors: Delisle, Samuel V., Labreche, Cedrik, Lara-Márquez, Mónica, Abou-Hamad, John, Garland, Brennan, Lamarche-Vane, Nathalie, Sabourin, Luc A.
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier B.V 01.10.2024
• Subjects: Kinase inactive; Migration; SLK; Ste20-like kinase; Stk2; Kinase inactive; SLK; Migration; Ste20-like kinase; Stk2
• ISSN: 0167-4889; 1879-2596; 1879-2596
• DOI: 10.1016/j.bbamcr.2024.119783

Kinases are known to have kinase activity independent functions. To gain further insights into potential kinase-independent functions of SLK/STK2, we have developed a kinase-dead allele, SLKK63R using in vivo CRISPR/Cas technology. Our studies show that blastocysts homozygote for SLKK63R do not develop into viable mice. However, heterozygotes are viable and fertile with no overt phenotypes. Analyses of mouse embryonic fibroblasts show that expression of SLKK63R results in a 50% decrease in kinase activity in heterozygotes. In contrast to previous studies, our data show that SLK does not form homodimers and that the kinase defective allele does not act in a dominant negative fashion. Expression of SLKK63R leads to altered Rac1 and RhoA activity, increased stress fiber formation and delayed focal adhesion turnover. Our data support a previously observed role for SLK in cell migration and suggest that at least 50% kinase activity is sufficient for embryonic development. •Mice homozygote for kinase dead SLK are not viable but heterozygotes are apparently normal.•Mouse embryonic fibroblasts expressing kinase inactive SLK show defects in focal adhesion turnover and motility.•Expression of kinase inactive SLK in mouse embryonic fibroblasts induces RhoA activity and stress fibers but inhibits Rac1.