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Insulin Substrate Receptor (IRS) proteins in normal and malignant hematopoiesis
Machado-Neto, João Agostinho; Fenerich, Bruna Alves; Rodrigues Alves, Ana Paula Nunes; Fernandes, Jaqueline Cristina; Scopim-Ribeiro, Renata; Coelho-Silva, Juan Luiz; Traina, Fabiola.
  • Machado-Neto, João Agostinho; Universidade de Sao Paulo. Faculdade de Medicina de Ribeirao Preto. Departamento de Medicina Interna. Ribeirao Preto. BR
  • Fenerich, Bruna Alves; Universidade de Sao Paulo. Faculdade de Medicina de Ribeirao Preto. Departamento de Medicina Interna. Ribeirao Preto. BR
  • Rodrigues Alves, Ana Paula Nunes; Universidade de Sao Paulo. Faculdade de Medicina de Ribeirao Preto. Departamento de Medicina Interna. Ribeirao Preto. BR
  • Fernandes, Jaqueline Cristina; Universidade de Sao Paulo. Faculdade de Medicina de Ribeirao Preto. Departamento de Medicina Interna. Ribeirao Preto. BR
  • Scopim-Ribeiro, Renata; Universidade de Sao Paulo. Faculdade de Medicina de Ribeirao Preto. Departamento de Medicina Interna. Ribeirao Preto. BR
  • Coelho-Silva, Juan Luiz; Universidade de Sao Paulo. Faculdade de Medicina de Ribeirao Preto. Departamento de Medicina Interna. Ribeirao Preto. BR
  • Traina, Fabiola; Universidade de Sao Paulo. Faculdade de Medicina de Ribeirao Preto. Departamento de Medicina Interna. Ribeirao Preto. BR
Clinics ; 73(supl.1): e566s, 2018. tab, graf
Article in English | LILACS | ID: biblio-974958
ABSTRACT
The insulin receptor substrate (IRS) proteins are a family of cytoplasmic proteins that integrate and coordinate the transmission of signals from the extracellular to the intracellular environment via transmembrane receptors, thus regulating cell growth, metabolism, survival and proliferation. The PI3K/AKT/mTOR and MAPK signaling pathways are the best-characterized downstream signaling pathways activated by IRS signaling (canonical pathways). However, novel signaling axes involving IRS proteins (noncanonical pathways) have recently been identified in solid tumor and hematologic neoplasm models. Insulin receptor substrate-1 (IRS1) and insulin receptor substrate-2 (IRS2) are the best-characterized IRS proteins in hematologic-related processes. IRS2 binds to important cellular receptors involved in normal hematopoiesis (EPOR, MPL and IGF1R). Moreover, the identification of IRS1/ABL1 and IRS2/JAK2V617F interactions and their functional consequences has opened a new frontier for investigating the roles of the IRS protein family in malignant hematopoiesis. Insulin receptor substrate-4 (IRS4) is absent in normal hematopoietic tissues but may be expressed under abnormal conditions. Moreover, insulin receptor substrate-5 (DOK4) and insulin receptor substrate-6 (DOK5) are linked to lymphocyte regulation. An improved understanding of the signaling pathways mediated by IRS proteins in hematopoiesis-related processes, along with the increased development of agonists and antagonists of these signaling axes, may generate new therapeutic approaches for hematological diseases. The scope of this review is to recapitulate and review the evidence for the functions of IRS proteins in normal and malignant hematopoiesis.
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Full text: Available Index: LILACS (Americas) Main subject: Signal Transduction / Leukemia, Lymphoid / Leukemia, Myeloid / Insulin Receptor Substrate Proteins / Hematopoiesis Limits: Humans Language: English Journal: Clinics Journal subject: Medicine Year: 2018 Type: Article Affiliation country: Brazil Institution/Affiliation country: Universidade de Sao Paulo/BR

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Full text: Available Index: LILACS (Americas) Main subject: Signal Transduction / Leukemia, Lymphoid / Leukemia, Myeloid / Insulin Receptor Substrate Proteins / Hematopoiesis Limits: Humans Language: English Journal: Clinics Journal subject: Medicine Year: 2018 Type: Article Affiliation country: Brazil Institution/Affiliation country: Universidade de Sao Paulo/BR