Studies on the activation mechanisms of MMP-2 and ADAM17: identification of regula...
| Full text | |
| Author(s): |
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]
Total Authors: 8
|
| Affiliation: | [1] CNPEM, LNBio, Lab Nacl Biociencias, BR-13083970 Campinas, SP - Brazil
Total Affiliations: 1
|
| Document type: | Journal article |
| Source: | JOURNAL OF PROTEOME RESEARCH; v. 13, n. 4, p. 2080-2093, APR 2014. |
| Web of Science Citations: | 20 |
| Abstract | |
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) | |
| FAPESP's process: | 09/54067-3 - Acquisition of a mass spectrometer coupled to a liquid chromatography system for increasing the capacity to meet the needs of users and for making new technologies available in the Laboratory of Mass Spectrometry |
| Grantee: | Adriana Franco Paes Leme |
| Support type: | Multi-user Equipment Program |
| FAPESP's process: | 11/22421-2 - Determination of cleavage sites of recombinant ADAM-17 in human cells |
| Grantee: | Rebeca Kawahara Sakuma |
| Support type: | Scholarships in Brazil - Doctorate (Direct) |
| FAPESP's process: | 10/19278-0 - Study of regulation of ADAMs in oral cancer |
| Grantee: | Adriana Franco Paes Leme |
| Support type: | Research Grants - Young Investigators Grants |
| FAPESP's process: | 09/53839-2 - Creation of a Digital Pathology Laboratory using a histological slidescanner |
| Grantee: | Oslei Paes de Almeida |
| Support type: | Multi-user Equipment Program |