Abstract
Previous studies have shown that Disabled-2 (DAB2) is up-regulated during megakaryocytic differentiation of human K562 cells. To delineate the consequences of DAB2 induction, a DNA vector-based small interfering RNA (siRNA) was designed to intervene in DAB2 expression. We found that DAB2 siRNA specifically inhibited DAB2 induction, resulting in the modulation of cell-cell adhesion and mitogen-activated protein kinase (MAPK) phosphorylation. The morphological changes and beta3 integrin expression associated with megakaryocytic differentiation were not affected. Since the MAPK pathway has been shown to involve DAB2 induction [Tseng et al., Biochem. Biophys. Res. Commun. 285 (2001) 129-135], our results suggest a reciprocal regulation between DAB2 and MAPK in the differentiation of K562 cells. In addition, we have demonstrated for the first time that DAB2 siRNA is a valuable tool for unveiling the biological consequences of DAB2 expression.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Adaptor Proteins, Signal Transducing
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Adaptor Proteins, Vesicular Transport*
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Apoptosis Regulatory Proteins
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Base Sequence
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Cell Adhesion*
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Cell Differentiation
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Cell Line
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Enzyme Activation
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Genes, Tumor Suppressor
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HL-60 Cells
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Humans
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K562 Cells
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Leukemia, Myeloid / metabolism
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Megakaryocytes / cytology
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Megakaryocytes / enzymology*
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Megakaryocytes / physiology*
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Mitogen-Activated Protein Kinase 1 / metabolism
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Mitogen-Activated Protein Kinase 3
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Mitogen-Activated Protein Kinases / metabolism*
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Phosphorylation
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Protein Biosynthesis
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Proteins / genetics*
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RNA, Small Interfering / genetics*
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Tumor Suppressor Proteins
Substances
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Adaptor Proteins, Signal Transducing
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Adaptor Proteins, Vesicular Transport
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Apoptosis Regulatory Proteins
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DAB2 protein, human
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Proteins
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RNA, Small Interfering
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Tumor Suppressor Proteins
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Mitogen-Activated Protein Kinase 1
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Mitogen-Activated Protein Kinase 3
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Mitogen-Activated Protein Kinases