Deciphering the Role of the ADAM17-Dependent Secretome in Cell Signaling

Autor(es)

Kawahara, Rebeca ^[1] ; Lima, Renato Niyama ^[1] ; Domingues, Romenia R. ^[1] ; Pauletti, Bianca Alves ^[1] ; Meirelles, Gabriela V. ^[1] ; Assis, Michelle ^[1] ; Migliorini Figueira, Ana Carolina ^[1] ; Paes Leme, Adriana Franco ^[1]

Afiliação do(s) autor(es)

^[1] CNPEM, LNBio, Lab Nacl Biociencias, BR-13083970 Campinas, SP - Brazil

• Tipo de documento: Artigo Científico
• Fonte: JOURNAL OF PROTEOME RESEARCH; v. 13, n. 4, p. 2080-2093, APR 2014.
• Citações Web of Science: 19

Resumo

ADAM17 has been initially identified as the main sheddase responsible for releasing the soluble form of a variety of cell-surface proteins, including growth factors, cytokines, cell adhesion molecules, and receptors, most of which are associated with pathological processes, including cancer and inflammation. However, the function and composition of the ADAM17-dependent secretome on a proteome-wide scale is poorly understood. In this study, we observed that the ADAM17-dependent secretome plays an important role in promoting cell proliferation and migration. To further demonstrate the repertoire of proteins involved in this cross-talk, we employed mass-spectrometry-based proteomics using nonmetabolic and metabolic labeling approaches to explore the secretome composition of wild-type and ADAM17(-/-) knockout mouse embryonic fibroblast (mEF) cells. Bioinformatic analyses indicated the differential regulation of 277 soluble proteins in the ADAM17-dependent secretome as well as novel direct ADAM17 cleavage substrates, such as mimecan and perlecan. Furthermore, we found that the ADAM17-dependent secretome promoted an opposite regulation of ERK and FAK pathways as well as PPAR gamma downstream activation. These findings demonstrated fine-tuning of cell signaling rendered by the soluble molecules mediated by ADAM17. (AU)

• Processo FAPESP: 09/54067-3 - EMU: aquisição de um espectrômetro de massas acoplado a cromatografia líquida para permitir ampliar a capacidade de atendimento de usuários e disponibilizar novas tecnologias no Laboratório de Espectrometria de Massas do Centro de Biologia Molecular Estrutural (ABTLUS)
• Beneficiário: Adriana Franco Paes Leme
• Linha de fomento: Auxílio à Pesquisa - Programa Equipamentos Multiusuários
• Processo FAPESP: 11/22421-2 - Determinação dos sítios de clivagens de alvos de ADAM-17 recombinante em cultura de células humanas
• Beneficiário: Rebeca Kawahara Sakuma
• Linha de fomento: Bolsas no Brasil - Doutorado Direto
• Processo FAPESP: 10/19278-0 - Estudo da regulação de ADAMs em câncer oral
• Beneficiário: Adriana Franco Paes Leme
• Linha de fomento: Auxílio à Pesquisa - Apoio a Jovens Pesquisadores
• Processo FAPESP: 09/53839-2 - Criação do Laboratório de Patologia Digital através do uso do escaneador de lâminas histológicas (Aperio® Scanscope CS)
• Beneficiário: Oslei Paes de Almeida
• Linha de fomento: Auxílio à Pesquisa - Programa Equipamentos Multiusuários