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Ventresca EM , Lecht S , Jakubowski P , Chiaverelli RA , Weaver M , Del Valle L , Ettinger K , Gincberg G , Priel A , Braiman A , Lazarovici P , Lelkes PI , Marcinkiewicz C
Association of p75(NTR) and alpha9beta1 integrin modulates NGF-dependent cellular responses
Cell Signal. 2015 Jun;27(6) :1225-36
PMID: 25748048 PMCID: PMC4409011
AbstractDirect interaction of alpha9beta1 integrin with nerve growth factor (NGF) has been previously reported to induce pro-proliferative and pro-survival activities of non-neuronal cells. We investigated participation of p75(NTR) in alpha9beta1 integrin-dependent cellular response to NGF stimulation. Using selective transfection of glioma cell lines with these receptors, we showed a strong, cation-independent association of alpha9 integrin subunit with p75(NTR) on the cellular membrane by selective immunoprecipitation experiments. The presence of the alpha9/p75(NTR) complex increases NGF-dependent cell adhesion, proliferation and migration. Other integrin subunits including beta1 were not found in complex with p75(NTR). FRET analysis indicated that p75(NTR) and alpha9 integrin subunit are not closely associated through their cytoplasmic domains, most probably because of the molecular interference with other cytoplasmic proteins such as paxillin. Interaction of alpha9beta1 integrin with another ligand, VCAM-1 was not modulated by the p75(NTR). alpha9/p75(NTR) complex elevated NGF-dependent activation of MAPK Erk1/2 arty for integrin that may create active complexes with other types of receptors belonging to the TNF superfamily.
NotesVentresca, Erin M Lecht, Shimon Jakubowski, Piotr Chiaverelli, Rachel A Weaver, Michael Del Valle, Luis Ettinger, Keren Gincberg, Galit Priel, Avi Braiman, Alex Lazarovici, Philip Lelkes, Peter I Marcinkiewicz, Cezary R01 CA133262/CA/NCI NIH HHS/United States R01CA133262/CA/NCI NIH HHS/United States Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't England Cell Signal. 2015 Jun;27(6):1225-36. doi: 10.1016/j.cellsig.2015.02.029. Epub 2015 Mar 5.