Gene Regulation by Nerve Growth Factor

Greene, Lloyd A.; Aletta, John M.; Burstein, David; Drexler, Steven; Greenberg, Matthew; Leonard, Debra G.B.; Ziff, Edward B.

doi:10.1007/978-3-642-70940-1_1

Cited by 51 publications

(77 citation statements)

References 22 publications

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“…Consistent with both of these response properties is our observation that the PDGF receptor mRNA level present in untreated NIH3T3 cells (no addition lane, Figure 2B) is roughly equivalent to the up-regulated level of PDGF receptor mRNA expressed by forskolin-treated Schwann cells. cAMP induction of many genes, including immediate-early response genes such as c-fos (Curran et al, 1984), is characteristically rapid and transient (Greenberg et al, 1985). cAMP induction of PDGF receptor mRNA exhibits neither of these properties.…”

Section: Resultsmentioning

confidence: 99%

Cell-specific cyclic AMP-mediated induction of the PDGF receptor.

1990

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Section: Resultsmentioning

confidence: 99%

Cell-specific cyclic AMP-mediated induction of the PDGF receptor.

1990

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“…This finding indicates that CBP, like its partner CREB, is a key target of the NGF-stimulated signaling pathway. NGF has been shown to induce differentiation of PC12 cells in part by stimulating the transcription of specific genes including c-fos (41). CBP has been shown to be essential for transcriptional induction of c-fos by NGF (16,34).…”

Section: Discussionmentioning

confidence: 99%

Nerve Growth Factor Up-regulates the Transcriptional Activity of CBP through Activation of the p42/p44MAPK Cascade

Liu

Chrivia

Latchman

1998

Journal of Biological Chemistry

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“…Expression of the immediate-early gene c-fos is rapidly induced in PC12 cells by a variety of extracellular stimuli, including NGF (21,43). The NGF signal is, in fact, transmitted into the nucleus and stimulates c-fos transcription by means of at least two Ras-dependent protein kinases as follows: ERK, which regulates the activity of transcription factor TCF/Elk-1, and a CREB kinase, which regulates the activity of CREB (29).…”

Section: Discussionmentioning

confidence: 99%

Abrogation of Nerve Growth Factor-induced Terminal Differentiation by ret Oncogene Involves Perturbation of Nuclear Translocation of ERK

Colucci-D'Amato¹,

D’Alessio²,

Califano³

et al. 2000

Journal of Biological Chemistry

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Oncogenic variants of the receptor tyrosine kinase, Ret, cause formation of tumors of neuroendocrine derivation in the multiple endocrine neoplasia type 2 and, thus, likely interfere with antiproliferative and/or differentiative extracellular signals. Here we took advantage of two rat pheochromocytoma-derived cell lines (PC12/MEN2A and PC12/MEN2B) to investigate whether Ret-induced nerve growth factor (NGF) unresponsiveness might involve impairment of ERK signaling. In fact, these cells, stably transfected with distinct forms of the active ret oncogene, fail to block proliferation, even upon NGF stimulation. In these cells we show the presence of both chronic ERKs activity and high expression levels of MKP-3, an ERK-specific phosphatase. Despite the presence of MKP-3, ERK activity can be further stimulated by NGF, but it fails to translocate into the nucleus and consequently to induce immediate-early gene transcription. Because of the presence of MKP-3, our results suggest the existence of a negative regulatory feedback acting on ERKs as a mechanism responsible for the abrogation of NGF-induced terminal differentiation. Indeed, MKP-3 seems to be implicated in the persistence of ERKs in cell cytoplasm. This interpretation is further supported by the observation that in ret-transfected cells, forced expression of an active form of MEK-1 may overcome this block; it restores transcription from the c-fos promoter, induces translocation of ERKs into the nucleus, and inhibits cell proliferation.Ret is a receptor tyrosine kinase whose expression is restricted to neuronal cells of the central and peripheral nervous system. Recently four ligands have been described for this receptor as follows: glial cell-derived neurotrophic factor, neurturin, artemin, and persephin (1).Germ line mutations of the receptor tyrosine kinase, Ret, are responsible for the multiple endocrine neoplasia (MEN) 1 type 2A and 2B syndrome and for the familial medullary thyroid carcinoma (2-5). MEN-2A and MEN-2B are distinct hereditary neoplastic syndromes both characterized by the presence of medullary thyroid carcinomas and pheochromocytomas (6, 7). Missense mutations at one of five cysteine residues (Cys-609, -611, -618, -620, and -634) clustered in the extra cytoplasmic domain of ret are the most frequent causative genetic events of familial medullary thyroid carcinoma and the MEN-2A syndrome (8). A single point mutation, which results in a Thr for Met substitution at codon 918 within the Ret catalytic domain, is responsible for the MEN-2B syndrome (8). These mutations convert ret into a dominant transforming gene and cause constitutive activation of its intrinsic tyrosine kinase activity, although their mechanism of activation differs (8 -10). In MEN-2 syndromes, the molecular mechanisms by which the mutated Ret contribute to the development of neuroendocrine neoplasms remain largely unknown. Indeed, the inheritance of mutated ret alleles implicates them in the pathogenesis of a generalized hyperplasia of the entire population of thyroid C-cells...

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Gene Regulation by Nerve Growth Factor

Cited by 51 publications

References 22 publications

Cell-specific cyclic AMP-mediated induction of the PDGF receptor.

Cell-specific cyclic AMP-mediated induction of the PDGF receptor.

Nerve Growth Factor Up-regulates the Transcriptional Activity of CBP through Activation of the p42/p44MAPK Cascade

Abrogation of Nerve Growth Factor-induced Terminal Differentiation by ret Oncogene Involves Perturbation of Nuclear Translocation of ERK

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