Imatinib restores VASP activity and its interaction with Zyxin in BCR-ABL leukemic cells

Autor(es)

Bernusso, Vanessa A. ^[1] ; Machado-Neto, Joao A. ^[1] ; Pericole, Fernando V. ^[1] ; Vieira, Karla P. ^[1] ; Duarte, Adriana S. S. ^[1] ; Traina, Fabiola ^[1] ; Hansen, Marc D. ^[2] ; Saad, Sara T. Olalla ^[1] ; Barcellos, Karin S. A. ^[1]

Afiliação do(s) autor(es)

^[1] Univ Estadual Campinas, Hematol & Hemotherapy Ctr, UNICAMP, Hemocentro, Inst Natl Ciencia & Tecnol Sangue, BR-13083878 Campinas, SP - Brazil

^[2] Brigham Young Univ, Dept Physiol & Dev Biol, Provo, UT 84602 - USA

• Tipo de documento: Artigo Científico
• Fonte: BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR CELL RESEARCH; v. 1853, n. 2, p. 388-395, FEB 2015.
• Citações Web of Science: 5

Resumo

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 phosphotylation 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 phosphotylation at Ser157 in VASP. (C) 2014 Elsevier B.V. All rights reserved. (AU)

• Processo FAPESP: 08/57895-1 - Instituto Nacional de Ciência e Tecnologia do Sangue
• Beneficiário: Sara Teresinha Olalla Saad
• Modalidade de apoio: Auxílio à Pesquisa - Temático
• Processo FAPESP: 11/51959-0 - Biologia das doenças neoplásicas da medula óssea
• Beneficiário: Sara Teresinha Olalla Saad
• Modalidade de apoio: Auxílio à Pesquisa - Temático
• Processo FAPESP: 07/53096-4 - Estudo da expressao das proteinas arhgap21 e b-catenina em celulas com ausencia de a-catenina.
• Beneficiário: Karin Spat Albino Barcellos Silveira
• Modalidade de apoio: Bolsas no Brasil - Pós-Doutorado
• Processo FAPESP: 11/14498-5 - Estudo da expressão e participação de vasp e zyxin na diferenciação hematopoiética, na leucemia mieloide crônica e na via de sinalização bcr-abl
• Beneficiário: Vanessa Aline Bernusso
• Modalidade de apoio: Bolsas no Brasil - Mestrado