Novel role of pleckstrin homology domain of the Bcr-Abl protein: analysis of protein-protein and protein-lipid interactions.
The Bcr-Abl protein is a marker for malignant transformation in chronic myeloid leukemia and in acute lymphoblastic leukemia. There are three Bcr-Abl chimeras known so far, p190, p210 and p230. The only structural difference between the three Bcr-Abl proteins is the presence of DH and PH domains from the Bcr gene in p210 and p230. The Bcr-Abl DH domain is functioning as a guanine nucleotide exchange factor for Rho family of small GTPases. The PH domain confers binding to phosphoinositides but some PH domains have also been found to bind specific target proteins. Here we show that the PH domain from Bcr-Abl binds a number of proteins involved in vital cellular processes. These proteins include PLCvarepsilon, Zizimin1, tubulin and SMC1. The revelation of the role of the Bcr-Abl PH domain in leukemogenesis is likely to provide clues to the molecular mechanisms underlying the phenotypes of Bcr-Abl positive leukemia and could therefore provide tools for the identification of targets for the development of therapeutic treatments.
Miroshnychenko
Daria
D
Institute of Molecular Biology and Genetics NAS of Ukraine, Zabolotnogo str, 150 Kyiv 03143, Ukraine.
Dubrovska
Anna
A
Maliuta
Stanislav
S
Telegeev
Gennady
G
Aspenström
Pontus
P
D000818:Animals; D015415:Biomarkers; D019556:COS Cells; D002460:Cell Line; D002522:Chlorocebus aethiops; D004591:Electrophoresis, Polyacrylamide Gel; D016313:Genes, abl / Q000235:genetics / Q000502:physiology*; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics / Q000502:physiology; D020014:K562 Cells; D008856:Microscopy, Fluorescence; D010716:Phosphatidylinositols / Q000378:metabolism*; D011485:Protein Binding; D040901:Proteomics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction
D015415:Biomarkers; D047908:Intracellular Signaling Peptides and Proteins; C418612:PHIP protein, human; D010716:Phosphatidylinositols