Src Signaling Regulates Completion of Abscission in Cytokinesis through ERK/MAPK Activation at the Midbody
| Autor: | Yoshimi Nakazato, Kousuke Kasahara, Naoto Yamaguchi, Kikuko Ikeda, Takahisa Kuga, Yuji Nakayama |
|---|---|
| Rok vydání: | 2007 |
| Předmět: |
G2 Phase
MAPK/ERK pathway MAP Kinase Signaling System Proto-Oncogene Proteins pp60(c-src) Cleavage furrow formation Biology Biochemistry chemistry.chemical_compound Humans Enzyme Inhibitors Phosphorylation Extracellular Signal-Regulated MAP Kinases Molecular Biology Cytokinesis Tyrosine phosphorylation Cell Biology Cell biology Enzyme Activation Protein Transport Midbody SU6656 chemistry rab GTP-Binding Proteins Cell Division HeLa Cells Proto-oncogene tyrosine-protein kinase Src |
| Zdroj: | Journal of Biological Chemistry. 282:5327-5339 |
| ISSN: | 0021-9258 |
| DOI: | 10.1074/jbc.m608396200 |
| Popis: | Src family non-receptor-type tyrosine kinases regulate a wide variety of cellular events including cell cycle progression in G(2)/M phase. Here, we show that Src signaling regulates the terminal step in cytokinesis called abscission in HeLa cells. Abscission failure with an unusually elongated intercellular bridge containing the midbody is induced by treatment with the chemical Src inhibitors PP2 and SU6656 or expression of membrane-anchored Csk chimeras. By anti-phosphotyrosine immunofluorescence and live cell imaging, completion of abscission requires Src-mediated tyrosine phosphorylation during early stages of mitosis (before cleavage furrow formation), which is subsequently delivered to the midbody through Rab11-driven vesicle transport. Treatment with U0126, a MEK inhibitor, decreases tyrosine phosphorylation levels at the midbody, leading to abscission failure. Activated ERK by MEK-catalyzed dual phosphorylation on threonine and tyrosine residues in the TEY sequence, which is strongly detected by anti-phosphotyrosine antibody, is transported to the midbody in a Rab11-dependent manner. Src kinase activity during the early mitosis mediates ERK activation in late cytokinesis, indicating that Src-mediated signaling for abscission is spatially and temporally transmitted. Thus, these results suggest that recruitment of activated ERK, which is phosphorylated by MEK downstream of Src kinases, to the midbody plays an important role in completion of abscission. |
| Databáze: | OpenAIRE |
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