Recruitment and activation of SLK at the leading edge of migrating cells requires Src family kinase activity and the LIM-only protein 4
| Autor: | Christopher J. Storbeck, Kyla D. Baron, Khalid N. Al-Zahrani, Luc A. Sabourin, Cédrik Labrèche, Jane E. Visvader, Jillian Conway |
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| Rok vydání: | 2015 |
| Předmět: |
Ldb1
c-Src Biology Protein Serine-Threonine Kinases SLK 3T3 cells Focal adhesion 03 medical and health sciences Mice 0302 clinical medicine Cell Movement medicine Animals Humans Src family kinase Pseudopodia Kinase activity Molecular Biology Migration 030304 developmental biology Adaptor Proteins Signal Transducing 0303 health sciences HEK 293 cells Signal transducing adaptor protein Cell migration 3T3 Cells Cell Biology Fibroblasts LIM Domain Proteins Cell biology Protein Structure Tertiary DNA-Binding Proteins Enzyme Activation Protein Transport medicine.anatomical_structure HEK293 Cells src-Family Kinases 030220 oncology & carcinogenesis Ste20-like kinase Cancer research Female LMO4 Gene Deletion Proto-oncogene tyrosine-protein kinase Src Protein Binding Subcellular Fractions |
| Zdroj: | Biochimica et Biophysica Acta (BBA) - Molecular Cell Research. 1853(7):1683-1692 |
| ISSN: | 0167-4889 |
| DOI: | 10.1016/j.bbamcr.2015.04.003 |
| Popis: | The Ste20-like kinase SLK plays a pivotal role in cell migration and focal adhesion turnover and is regulated by the LIM domain-binding proteins Ldb1 and Ldb2. These adapter proteins have been demonstrated to interact with LMO4 in the organization of transcriptional complexes. Therefore, we have assessed the ability of LMO4 to also interact and regulate SLK activity. Our data show that LMO4 can directly bind to SLK and activate its kinase activity in vitro and in vivo. LMO4 can be co-precipitated with SLK following the induction of cell migration by scratch wounding and Cre-mediated deletion of LMO4 in conditional LMO4fl/fl fibroblasts inhibits cell migration and SLK activation. Deletion of LMO4 impairs Ldb1 and SLK recruitment to the leading edge of migrating cells. Supporting this, Src/Yes/Fyn-deficient cells (SYF) expressing very low levels of LMO4 do not recruit SLK to the leading edge. Re-expression of wildtype Myc–LMO4 in SYF cells, but not a mutant version, restores SLK localization and kinase activity. Overall, our data suggest that activation of SLK by haptotactic signals requires its recruitment to the leading edge by LMO4 in a Src-dependent manner. Furthermore, this establishes a novel cytosolic role for the transcriptional co-activator LMO4. |
| Databáze: | OpenAIRE |
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