Molecular mechanisms of regulation of phosphoinositide 3-kinase by insulin, insulin-like growth factor I and nerve growth factor in PC12 cells

1995 ◽  
Vol 23 (1) ◽  
pp. 148-152 ◽  
Author(s):  
A. N. Carter ◽  
C. P. Downes
Keyword(s):  
Nerve Growth Factor ◽  
Growth Factor ◽  
Pc12 Cells ◽  
Molecular Mechanisms ◽  
Insulin Like Growth Factor ◽  
Nerve Growth ◽  
Factor I ◽  
Growth Factor I ◽  
Phosphoinositide 3 Kinase

Interactions of estrogen and insulin-like growth factor-I in the brain: molecular mechanisms and functional implications

2002 ◽  
Vol 83 (1-5) ◽  
pp. 211-217 ◽  
Author(s):  
Gloria Patricia Cardona-Gómez ◽  
Pablo Mendez ◽  
Lydia L. DonCarlos ◽  
Iñigo Azcoitia ◽  
Luis M. Garcia-Segura
Keyword(s):  
Growth Factor ◽  
Molecular Mechanisms ◽  
Insulin Like Growth Factor ◽  
Factor I ◽  
Functional Implications ◽  
Growth Factor I ◽  
The Brain

scholarly journals Role of Phosphoinositide 3-Kinase and Endocytosis in Nerve Growth Factor-Induced Extracellular Signal-Regulated Kinase Activation via Ras and Rap1

2000 ◽  
Vol 20 (21) ◽  
pp. 8069-8083 ◽  
Author(s):  
Randall D. York ◽  
Derek C. Molliver ◽  
Savraj S. Grewal ◽  
Paula E. Stenberg ◽  
Edwin W. McCleskey ◽  
...  
Keyword(s):  
Nerve Growth Factor ◽  
Growth Factor ◽  
Map Kinase ◽  
Pc12 Cells ◽  
Erk Signaling ◽  
Nerve Growth ◽  
Erk Activation ◽  
Extracellular Signal Regulated Kinase ◽  
Extracellular Signal ◽  
Phosphoinositide 3 Kinase

ABSTRACT Neurotrophins promote multiple actions on neuronal cells including cell survival and differentiation. The best-studied neurotrophin, nerve growth factor (NGF), is a major survival factor in sympathetic and sensory neurons and promotes differentiation in a well-studied model system, PC12 cells. To mediate these actions, NGF binds to the TrkA receptor to trigger intracellular signaling cascades. Two kinases whose activities mediate these processes include the mitogen-activated protein (MAP) kinase (or extracellular signal-regulated kinase [ERK]) and phosphoinositide 3-kinase (PI3-K). To examine potential interactions between the ERK and PI3-K pathways, we studied the requirement of PI3-K for NGF activation of the ERK signaling cascade in dorsal root ganglion cells and PC12 cells. We show that PI3-K is required for TrkA internalization and participates in NGF signaling to ERKs via distinct actions on the small G proteins Ras and Rap1. In PC12 cells, NGF activates Ras and Rap1 to elicit the rapid and sustained activation of ERKs respectively. We show here that Rap1 activation requires both TrkA internalization and PI3-K, whereas Ras activation requires neither TrkA internalization nor PI3-K. Both inhibitors of PI3-K and inhibitors of endocytosis prevent GTP loading of Rap1 and block sustained ERK activation by NGF. PI3-K and endocytosis may also regulate ERK signaling at a second site downstream of Ras, since both rapid ERK activation and the Ras-dependent activation of the MAP kinase kinase kinase B-Raf are blocked by inhibition of either PI3-K or endocytosis. The results of this study suggest that PI3-K may be required for the signals initiated by TrkA internalization and demonstrate that specific endocytic events may distinguish ERK signaling via Rap1 and Ras.

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