Dissecting the Mode of Action of a Neuronal Growth Factor

Halegoua, Simon; Armstrong, Robert C.; Kremer, Norbert E.

doi:10.1007/978-3-642-75747-1_7

Cited by 132 publications

(133 citation statements)

References 215 publications

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“…For example, induction of genes encoding neurofilament-L, acetylcholinesterase, GAP-43, and nicotinic AChR, is first seen at 24 -48 h, whereas muscarinic and enkephalin receptors, synapsin, Na/K ATPase, and the neurofilament protein peripherin occurs 48 -96 h following exposure to NGF (for review see Ref. 31). We conclude, therefore, that (Fig.…”

Section: Discussionmentioning

confidence: 99%

Selective Regulation of Agrin mRNA Induction and Alternative Splicing in PC12 Cells by Ras-dependent Actions of Nerve Growth Factor

Smith¹,

Fanger²,

O'Connor³

et al. 1997

Journal of Biological Chemistry

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The extracellular matrix protein agrin plays an important role in the formation and maintenance of the neuromuscular junction. However, regulation of agrin gene expression and pre-mRNA splicing, important in determining the biological actions of agrin, is not well understood. To begin to identify mechanisms controlling agrin expression, quantitative polymerase chain reaction techniques were used to analyze the effect of growth factors on the expression of agrin mRNA isoforms in rat pheochromocytoma (PC12) cells. Agrin transcripts in untreated cells lacked inserts in the Y and Z sites (agrin y0z0 ), encoding agrin isoforms with low acetylcholine receptor aggregating activity and a primarily non-neuronal tissue distribution. Transcripts encoding isoforms with high aggregating activity and neuronal tissue distribution (agrin y4z8 , agrin y4z11 , and agrin y4z19 ) were not detected. Treatment of PC12 cells with nerve growth factor (NGF) caused a significant increase in total agrin mRNA. In contrast, exposure to epidermal growth factor had no effect. Analysis of alternative splicing of agrin mRNA revealed that NGF elicited a specific increase in agrin y4 and agrin z8 mRNAs that did not occur in the presence of epidermal growth factor, insulin, dexamethasone, or retinoic acid. Analysis of PC12 sublines stably overexpressing a dominant inhibitory form of p21 Ras indicated that NGF induced changes in levels of agrin mRNA and alternative splicing required Ras activity. The results show that NGF can influence important aspects of neuronal differentiation by regulating alternative splicing. Furthermore, these data provide insight into the mechanisms governing agrin gene expression and suggest that neurotrophic factors may play a role in regulating agrin expression in vivo.

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Section: Discussionmentioning

confidence: 99%

Selective Regulation of Agrin mRNA Induction and Alternative Splicing in PC12 Cells by Ras-dependent Actions of Nerve Growth Factor

Smith¹,

Fanger²,

O'Connor³

et al. 1997

Journal of Biological Chemistry

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“…This cell line has characteristics of precursor cells for both sympathetic neurons and chroma n cells. Incubation of PC12 cells with nerve growth factor (NGF) or other neurotrophic factors leads to biochemical and morphological changes characteristic of sympathetic neuronal cell di erentiation including neurite extension, cessation of cell division and expression of neuronal-speci®c genes (for a review see Halegoua et al, 1991).…”

Section: Introductionmentioning

confidence: 99%

Retinoic acid induces secretion of transforming growth factors by PC12 pheochromocytoma cells

1997

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“…It can also promote the di erentiation of PC12 cells to acquire characteristics of sympathetic neurons (Green and Tischler, 1976). PC12 cells have been useful as a model to investigate cellular di erentiation induced by NGF and ®broblast growth factor (FGF) (Green and Tischler, 1976;Halegoua et al, 1991) as well as proliferation induced by epidermal growth factor (EGF) (Greene and Tischler, 1976). NGF stimulation induces receptor dimerization and autophosphorylation on tyrosine (Kaplan et al, 1991a,b), which in turn induces a signalling cascade (reviewed in Kaplan and Miller, 1997).…”

mentioning

confidence: 99%

c-abl is involved in the association of p53 and trk A

et al. 2000

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The p53 tumour suppressor phosphoprotein associates with proteins involved in DNA replication, transcription, cell cycle machinery and regulation of its own expression. Recently it has been shown that p53 can also bind to trk A tyrosine kinase which is the receptor for nerve growth factor (NGF). This study demonstrates that p53 appears to associate with trk A via c-abl. Endogenous cabl was detected when the trk A and p53 complex was immunoprecipitated from lysates of NGF stimulated NIH3T3 cells expressing trk A or NIH3T3 cells expressing trk A and a temperature sensitive p53 (val 135). Endogenous c-abl and trk A association was observed in NGF stimulated p53 negative ®broblasts transfected with trk A alone; suggesting that c-abl can independently bind to trk A in the absence of p53. Interestingly, association between endogenous p53 and trk A was not detected in NGF stimulated abl negative ®broblasts transfected with trk A or when these cells were exposed to gamma radiation. This result suggests that p53 preferentially binds to trk A in the presence of c-abl and that p53 and trk A do not appear to associate directly even if p53 is activated and its levels increased by gamma radiation. Overall, these data suggest that cabl is possibly acting as an adaptor or bridge between p53 and trk A. Oncogene (2000) 19, 3032 ± 3040.

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Dissecting the Mode of Action of a Neuronal Growth Factor

Cited by 132 publications

References 215 publications

Selective Regulation of Agrin mRNA Induction and Alternative Splicing in PC12 Cells by Ras-dependent Actions of Nerve Growth Factor

Selective Regulation of Agrin mRNA Induction and Alternative Splicing in PC12 Cells by Ras-dependent Actions of Nerve Growth Factor

Retinoic acid induces secretion of transforming growth factors by PC12 pheochromocytoma cells

c-abl is involved in the association of p53 and trk A

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