S-Space College of Medicine/School of Medicine (의과대학/대학원) Molecular and Genomic Medicine (분자유전체의학전공) Journal Papers (저널논문_분자유전체의학전공)
Differential tyrosine phosphorylation of leukemic cells during apoptosis as a result of treatment with imatinib mesylate
- Park, Jungeun; Kim, Sangmi; Oh, Chongkil; Yoon, Sung Soo; Lee, Dongsoon; Kim, Youngsoo
- Issue Date
- Biochem Biophys Res Commun. 2005 Oct 28;336(3):942-51.
- Antineoplastic Agents/*pharmacology; *Apoptosis; Blotting, Western; Cell Cycle/drug effects; Cell Cycle Proteins/genetics/metabolism; Cell Proliferation/drug effects; Electrophoresis, Gel, Two-Dimensional; Fusion Proteins, bcr-abl/*antagonists & inhibitors; Humans; K562 Cells; Leukemia, Myelogenous, Chronic, BCR-ABL; Positive/*enzymology/metabolism/pathology; Phosphorylation; Piperazines/*pharmacology; Protein Kinase Inhibitors/*pharmacology; Proteome/metabolism; Pyrimidines/*pharmacology; Transcription, Genetic/drug effects; Tyrosine/metabolism
- Bcr-Abl fusion tyrosine kinase contributes to leukemic transformation. Imatinib mesylate inhibits Bcr-Abl tyrosine kinase, resulting in a blockage of tyrosine phosphorylation in its downstream pathways. We analyzed the alteration of tyrosine phosphorylation, on BCR/ABL+ chronic myelogenous leukemia cells, after treatment with imatinib mesylate. Data were collected using a two-dimensional gel electrophoresis followed by Western blot and mass spectrometry. The inhibition of Bcr-Abl tyrosine kinase by 2.5 microM imatinib mesylate caused both cell cycle arrest in the G0/G1 phase and increased the portion of apoptotic cells. As a result, the population of leukemic cells decreased by 30% and 70% compared to controls at 24 and 72 h, respectively. Furthermore, treatment with imatinib mesylate altered tyrosine phosphorylation of 24 protein spots as the incubation time proceeded from 0 to 24 and 72 h. Ten of the 24 protein spots are visible at all three times. Four are detectable at both the 0 and 24 h points in time. Eight were detectable only at time 0.
- 0006-291X (Print)
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