Mst1 Kinase Regulates the Actin-Bundling Protein L-Plastin To Promote T Cell Migration
| Autor: | Jiancheng Hu, Xinxin Wang, Jennifer L. Vella, Xiaolu Xu, Yunfeng Feng, Yina H. Huang, John A. Cooper, Sharon Celeste Morley, Elizabeth M. Todd, Olivia L. Mooren, Emily R. Jaeger |
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| Rok vydání: | 2016 |
| Předmět: |
0301 basic medicine
MST1 T-Lymphocytes Lymphocyte Immunology Protein Serine-Threonine Kinases Biology Lymphocyte Activation Article Mice 03 medical and health sciences Cell Movement medicine Animals Immunology and Allergy Lymphocytes Pseudopodia Phosphorylation Kinase Microfilament Proteins digestive oral and skin physiology nutritional and metabolic diseases Cell migration Flow Cytometry Phosphoproteins Cell biology Cytoskeletal Proteins Protein Transport 030104 developmental biology medicine.anatomical_structure T cell migration Cancer research lipids (amino acids peptides and proteins) Signal transduction Lamellipodium Signal Transduction |
| Zdroj: | The Journal of Immunology. 197:1683-1691 |
| ISSN: | 1550-6606 0022-1767 |
| Popis: | Exploring the mechanisms controlling lymphocyte trafficking is essential for understanding the function of the immune system and the pathophysiology of immunodeficiencies. The mammalian Ste20–like kinase 1 (Mst1) has been identified as a critical signaling mediator of T cell migration, and loss of Mst1 results in immunodeficiency disease. Although Mst1 is known to support T cell migration through induction of cell polarization and lamellipodial formation, the downstream effectors of Mst1 are incompletely defined. Mice deficient for the actin-bundling protein L-plastin (LPL) have phenotypes similar to mice lacking Mst1, including decreased T cell polarization, lamellipodial formation, and cell migration. We therefore asked whether LPL functions downstream of Mst1. The regulatory N-terminal domain of LPL contains a consensus Mst1 phosphorylation site at Thr89. We found that Mst1 can phosphorylate LPL in vitro and that Mst1 can interact with LPL in cells. Removal of the Mst1 phosphorylation site by mutating Thr89 to Ala impaired localization of LPL to the actin-rich lamellipodia of T cells. Expression of the T89A LPL mutant failed to restore migration of LPL-deficient T cells in vitro. Furthermore, expression of T89A LPL in LPL-deficient hematopoietic cells, using bone marrow chimeras, failed to rescue the phenotype of decreased thymic egress. These results identify LPL as a key effector of Mst1 and establish a novel mechanism linking a signaling intermediate to an actin-binding protein critical to T cell migration. |
| Databáze: | OpenAIRE |
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