We have previously demonstrated that although LOK is the dominant ERM kinase in lymphocytes, some ERM phosphorylation remains in LOK-knockout mice. We postulate that this residual phosphorylation is mediated by the kinase SLK, which is the most closely related to LOK and is expressed in lymphocytes. We are using the most powerful approach available, knockout mice, to assess the biological importance of SLK in intact animals. We have generated a conditional SLK-knockout mouse and have confirmed by breeding that the conventional knockout is embryonic lethal. Breeding is well along for generation of a mice in whose T-cells SLK is deleted (using lck-Cre), which will also be crossed to LOK knockout mice. We will test immune system development and T-cell phenotype/function especially as it relates to ERM phosphorylation.
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|Belkina, Natalya V; Liu, Yin; Hao, Jian-Jiang et al. (2009) LOK is a major ERM kinase in resting lymphocytes and regulates cytoskeletal rearrangement through ERM phosphorylation. Proc Natl Acad Sci U S A 106:4707-12|