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Partners of wild type Grb7 and a mutant lacking its calmodulin-binding domain

Abstract

Growth factor receptor bound protein 7 (Grb7) is a mammalian adaptor protein participating in signaling pathways implicated in cell migration, metastatic invasion, cell proliferation and tumor-associated angiogenesis. We expressed tagged versions of wild type Grb7 and the mutant Grb7Delta, lacking its calmodulin-binding domain (CaM-BD), in human embryonic kidney (HEK) 293 cells and rat glioma C6 cells to identify novel binding partners using shot-gun proteomics. Among the new identified proteins, we validated the ubiquitin-ligase Nedd4 (neural precursor cell expressed developmentally down-regulated protein 4), the heat-shock protein Hsc70/HSPA8 (heat shock cognate protein 70) and the cell cycle regulatory protein caprin-1 (cytoplasmic activation/proliferation-associated protein 1) in rat glioma C6 cells. Our results suggest a role of Grb7 in pathways where these proteins are implicated. These include protein trafficking and degradation, stress-response, chaperone-mediated autophagy, apoptosis and cell proliferation.

Type Journal
ISBN 1096-0384 (Electronic) 0003-9861 (Linking)
Authors Garcia-Palmero, I.; Shah, N.; Ali, N. A.; Daly, R. J.; Wilce, J. A.; Villalobo, A.
Publisher Name ARCHIVES OF BIOCHEMISTRY AND BIOPHYSICS
Published Date 2020-07-31
Published Volume 687
Published Pages 108386
Status Published in-print
DOI 10.1016/j.abb.2020.108386
URL link to publisher's version https://www.ncbi.nlm.nih.gov/pubmed/32360748