Grb2-associated binder-1 mediates phosphatidylinositol 3-kinase activation and the promotion of cell survival by nerve growth factor
M Holgado-Madruga, DK Moscatello… - Proceedings of the …, 1997 - National Acad Sciences
M Holgado-Madruga, DK Moscatello, DR Emlet, R Dieterich, AJ Wong
Proceedings of the National Academy of Sciences, 1997•National Acad SciencesNerve growth factor (NGF) prevents apoptosis through stimulation of the TrkA receptor
protein tyrosine kinase. The downstream activation of phosphatidylinositol 3-kinase (PI 3-
kinase) is essential for the inhibition of apoptosis, although this enzyme does not bind to and
is not directly activated by TrkA. We have found that the addition of NGF to PC-12 cells
resulted in the phosphorylation of the Grb2-associated binder-1 (Gab1) docking protein and
induced the association of several SH2 domain-containing proteins, including PI 3-kinase. A …
protein tyrosine kinase. The downstream activation of phosphatidylinositol 3-kinase (PI 3-
kinase) is essential for the inhibition of apoptosis, although this enzyme does not bind to and
is not directly activated by TrkA. We have found that the addition of NGF to PC-12 cells
resulted in the phosphorylation of the Grb2-associated binder-1 (Gab1) docking protein and
induced the association of several SH2 domain-containing proteins, including PI 3-kinase. A …
Nerve growth factor (NGF) prevents apoptosis through stimulation of the TrkA receptor protein tyrosine kinase. The downstream activation of phosphatidylinositol 3-kinase (PI 3-kinase) is essential for the inhibition of apoptosis, although this enzyme does not bind to and is not directly activated by TrkA. We have found that the addition of NGF to PC-12 cells resulted in the phosphorylation of the Grb2-associated binder-1 (Gab1) docking protein and induced the association of several SH2 domain-containing proteins, including PI 3-kinase. A substantial fraction of the total cellular PI 3-kinase activity was associated with Gab1. PC-12 cells that overexpressed Gab1 show a decreased requirement for the amount of NGF necessary to inhibit apoptosis. The expression of a Gab1 mutant that lacked the binding sites for PI 3-kinase enhanced apoptosis and diminished the protective effect of NGF. Hence, Gab1 has a major role in connecting TrkA with PI 3-kinase activation and for the promotion of cell survival by NGF.
National Acad Sciences