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Investigation of IRS2 protein function in hematopoietic cells

Grant number: 14/23092-0
Support type:Scholarships in Brazil - Post-Doctorate
Effective date (Start): April 01, 2015
Effective date (End): November 30, 2017
Field of knowledge:Health Sciences - Medicine
Cooperation agreement: Coordination of Improvement of Higher Education Personnel (CAPES)
Principal Investigator:Fabíola Traina
Grantee:João Agostinho Machado Neto
Home Institution: Faculdade de Medicina de Ribeirão Preto (FMRP). Universidade de São Paulo (USP). Ribeirão Preto , SP, Brazil

Abstract

The insulin receptor substrate (IRS) comprise a family of cytoplasmic adapter proteins that recruit effector proteins involved in cellular signaling pathways, including PI3K/Akt, MAP kinase and JAK/STAT, and were initially characterized in insulin signaling. The insulin receptor substrate 2 (IRS2) may also be activated through its association with three growth factors receptors important for hematopoiesis: erythropoietin receptor (EPOR), thrombopoietin (MPL) and IGF1 receptor (IGF1R). Previous studies conducted by our research group indicate that IRS2 is recruited during the process of erythroid, megakaryocytic and granulocytic differentiation, participates in signal transduction of aberrant signaling induced by JAK2V617F mutation and is differentially expressed in hematologic malignancies, including myelodysplastic syndromes and acute leukemias. However, the role of IRS2 in signal transduction of hematopoietic growth factor receptors and their participation in cell differentiation and malignant transformation of hematopoietic cells remains largely unexplored. The aim of this study is to identify the specific functions of IRS2 in survival, proliferation, cell differentiation, and signal transduction, as well as, the identification of new compounds able to inhibit or stimulate signaling pathways mediated by IRS2 in hematopoiesis using IRS2 knockout animals and human cell lines. (AU)

Scientific publications
(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)
MACHADO-NETO, JOAO AGOSTINHO; FENERICH, BRUNA ALVES; SCOPIM-RIBEIRO, RENATA; EIDE, CHRISTOPHER A.; COELHO-SILVA, JUAN LUIZ; PORTO DECHANDT, CARLOS ROBERTO; FERNANDES, JAQUELINE CRISTINA; NUNES RODRIGUES ALVES, ANA PAULA; SCHEUCHER, PRISCILA SANTOS; SIMOES, BELINDA PINTO; ALBERICI, LUCIANE CARLA; DE FIGUEIREDO PONTES, LORENA LOBO; TOGNON, CRISTINA E.; DRUKER, BRIAN J.; REGO, EDUARDO MAGALHAES; TRAINA, FABIOLA. Metformin exerts multitarget antileukemia activity in JAK2(V617F)-positive myeloproliferative neoplasms. CELL DEATH & DISEASE, v. 9, FEB 22 2018. Web of Science Citations: 1.
MACHADO-NETO, JOAO AGOSTINHO; CAMPOS, PAULA DE MELO; FAVARO, PATRICIA; LAZARINI, MARIANA; SANTOS DUARTE, ADRIANA DA SILVA; LORAND-METZE, IRENE; COSTA, FERNANDO FERREIRA; OLALLA SAAD, SARA TERESINHA; TRAINA, FABIOLA. Stathmin 1 inhibition amplifies ruxolitinib-induced apoptosis in JAK2(V617F) cells. ONCOTARGET, v. 6, n. 30, p. 29573-29584, OCT 6 2015. Web of Science Citations: 7.

Please report errors in scientific publications list by writing to: cdi@fapesp.br.