Please use this identifier to cite or link to this item: http://repositorio.unicamp.br/jspui/handle/REPOSIP/85183
Type: Artigo de periódico
Title: Imatinib Restores Vasp Activity And Its Interaction With Zyxin In Bcr-abl Leukemic Cells
Author: Bernusso V.A.
Machado-Neto J.A.
Pericole F.V.
Vieira K.P.
Duarte A.S.S.
Traina F.
Hansen M.D.
Olalla Saad S.T.
Barcellos K.S.A.
Abstract: Vasodilator-stimulated phosphoprotein (VASP) and Zyxin are interacting proteins involved in cellular adhesion and motility. PKA phosphorylates VASP at serine 157, regulating VASP cellular functions. VASP interacts with ABL and is a substrate of the BCR-ABL oncoprotein. The presence of BCR-ABL protein drives oncogenesis in patients with chronic myeloid leukemia (CML) due to a constitutive activation of tyrosine kinase activity. However, the function of VASP and Zyxin in BCR-ABL pathway and the role of VASP in CML cells remain unknown. In vitro experiments using K562 cells showed the involvement of VASP in BCR-ABL signaling. VASP and Zyxin inhibition decreased the expression of anti-apoptotic proteins, BCL2 and BCL-XL. Imatinib induced an increase in phosphorylation at Ser157 of VASP and decreased VASP and BCR-ABL interaction. VASP did not interact with Zyxin in K562 cells; however, after Imatinib treatment, this interaction was restored. Corroborating our data, we demonstrated the absence of phosphorylation at Ser157 in VASP in the bone marrow of CML patients, in contrast to healthy donors. Phosphorylation of VASP on Ser157 was restored in Imatinib responsive patients though not in the resistant patients. Therefore, we herein identified a possible role of VASP in CML pathogenesis, through the regulation of BCR-ABL effector proteins or the absence of phosphorylation at Ser157 in VASP.
Editor: Elsevier
Rights: fechado
Identifier DOI: 10.1016/j.bbamcr.2014.11.008
Address: http://www.scopus.com/inward/record.url?eid=2-s2.0-84914133165&partnerID=40&md5=e264df12d6c40d2aaf666716c89f5847
Date Issue: 2015
Appears in Collections:Unicamp - Artigos e Outros Documentos

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