Disabled-2 small interfering RNA modulates cellular adhesive function and MAPK activity during megakaryocytic differentiation of K562 cells.
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.
Tseng
Ching-Ping
CP
Graduate Institute of Medical Biotechnology Chang Gung University, Kweishan, Taoyuan, Taiwan. ctseng@mail.cgu.edu.tw
Huang
Chien-Ling
CL
Huang
Ching-Hui
CH
Cheng
Ju-Chien
JC
Stern
Arnold
A
Tseng
Chin-Hsiao
CH
Chiu
Daniel Tsun-Yee
DT
D048868:Adaptor Proteins, Signal Transducing; D033942:Adaptor Proteins, Vesicular Transport; D051017:Apoptosis Regulatory Proteins; D001483:Base Sequence; D002448:Cell Adhesion; D002454:Cell Differentiation; D002460:Cell Line; D004789:Enzyme Activation; D016147:Genes, Tumor Suppressor; D018922:HL-60 Cells; D006801:Humans; D020014:K562 Cells; D007951:Leukemia, Myeloid / Q000378:metabolism; D008533:Megakaryocytes / Q000166:cytology / Q000201:enzymology* / Q000502:physiology*; D019950:Mitogen-Activated Protein Kinase 1 / Q000378:metabolism; D048052:Mitogen-Activated Protein Kinase 3; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism*; D010766:Phosphorylation; D014176:Protein Biosynthesis; D011506:Proteins / Q000235:genetics*; D034741:RNA, Small Interfering / Q000235:genetics*; D025521:Tumor Suppressor Proteins
D048868:Adaptor Proteins, Signal Transducing; D033942:Adaptor Proteins, Vesicular Transport; D051017:Apoptosis Regulatory Proteins; C102885:DAB2 protein, human; D011506:Proteins; D034741:RNA, Small Interfering; D025521:Tumor Suppressor Proteins; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3; D020928:Mitogen-Activated Protein Kinases