Induction of ornithine decarboxylase by nerve growth factor dissociated from effects on survival and neurite outgrowth

Greene, Lloyd A.; McGuire, Jeffrey C.

doi:10.1038/276191a0

Cited by 110 publications

(68 citation statements)

References 19 publications

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“…The position of the TATAAA box in relation to the transcription start site is shown. treatment has been disassociated from the actions of NGF that result in the neuronal differentiation of PC12 cells (38), and the distribution of ODC mRNA is not limited to nervous tissues.…”

Section: Discussionmentioning

confidence: 99%

Structure of the gene encoding VGF, a nervous system-specific mRNA that is rapidly and selectively induced by nerve growth factor in PC12 cells.

1991

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Nerve growth factor (NGF) plays a critical role in the development and survival of neurons in the peripheral nervous system. Following treatment with NGF but not epidermal growth factor, rat pheochromocytoma (PC12) cells undergo neural differentiation. We have cloned a nervous system-specific mRNA, NGF33.1, that is rapidly and relatively selectively induced by treatment of PC12 cells with NGF and basic fibroblast growth factor in comparison with epidermal growth factor. Analysis of the nucleic acid and predicted amino acid sequences of the NGF33.1 cDNA clone suggested that this clone corresponded to the NGF-inducible mRNA called VGF (A. Levi, J. D. Eldridge, and B. M. Paterson, Science 229:393-395, 1985; R. Possenti, J. D. Eldridge, B. M. Paterson, A. Grasso, and A. Levi, EMBO J. 8:2217-2223, 1989). We have used the NGF33.1 cDNA clone to isolate and characterize the VGF gene, and in this paper we report the complete sequence of the VGF gene, including 853 bases of 5' flank revealed TATAA and CCAAT elements, several GC boxes, and a consensus cyclic AMP response element-binding protein binding site. The VGF promoter contains sequences homologous to other NGF-inducible, neuronal promoters. We further show that VGF mRNA is induced in PC12 cells to a greater extent by depolarization and by phorbol-12-myristate-13-acetate treatment than by 8-bromo-cyclic AMP treatment. By Northern (RNA) and RNase protection analysis, VGF mRNA is detectable in embryonic and postnatal central and peripheral nervous tissues but not in a number of nonneural tissues. In the cascade of events which ultimately leads to the neural differentiation of NGF-treated PC12 cells, the VGF gene encodes the most rapidly and selectively regulated, nervous-system specific mRNA yet identified.

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Section: Discussionmentioning

confidence: 99%

Structure of the gene encoding VGF, a nervous system-specific mRNA that is rapidly and selectively induced by nerve growth factor in PC12 cells.

1991

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“…As shown in Fig. 7B (19,23,24,26 (4,23,66,74). We made the surprising observation that the FosER.pro protein, in contrast to the FosER(wt) protein, repressed the induction of ODC by NGF (Fig.…”

mentioning

confidence: 94%

Direct transcriptional stimulation of the ornithine decarboxylase gene by Fos in PC12 cells but not in fibroblasts.

Wrighton¹,

Busslinger²

1993

Mol. Cell. Biol.

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We have established rat PC12 pheochromocytoma cell lines stably expressing the estrogen-activatable transcription factor FosER to identify genes that can be regulated by c-Fos in this neuronal cell type. Induction of ectopic c-Fos activity in PC12 cells increased the mRNA levels of the ornithine decarboxylase (ODC) and tyrosine hydroxylase genes with similar kinetics and to the same maximal level as nerve growth factor treatment. In both cases the rate of transcription initiation was increased. Induction of the ODC gene occurred even in the absence of protein synthesis, indicating direct regulation by FosER. ODC expression, however, was not induced by a mutant FosER protein containing a proline insertion in the basic region of the c-Fos moiety, demonstrating the requirement for a functional DNA-binding domain. These data show that FosER, and by extrapolation c-Fos, can directly activate transcription of the endogenous ODC gene in PC12 cells by binding to cis-regulatory sequences. Activation of the ODC gene was unexpectedly transient, as transcripts returned to the basal level after prolonged exposure of PC12 cells to FosER activity. Furthermore, ODC transcription was not at all induced by FosER in rat fibroblasts. To account for this cell-specific action of FosER, we propose that stimulation of the ODC gene by FosER requires either (i) cooperation with another transcription factor(s) or (ii) a specific pattern of modification which is present in PC12 cells but not in otherwise unstimulated fibroblasts. One or both of these mechanisms may be employed by cells to achieve selective gene activation in response to apparently stereotyped induction of c-fos.

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“…Most importantly, no induction of c-fos was observed with either trkB.T1 or trkB.T2 transfected cells treated with BDNF. We also examined another common receptor tyrosine kinase-mediated response, the induction of ornithine decarboxylase activity (Greene et al, 1978;Guroff et al, 1981;Feinstein et al, 1985). Again, trkB.FL transfectants, but not trkB.T1 or trkB.T2 transfectants, responded to BDNF treatment (data not shown).…”

Section: Transfected Cells Expressing Trkbt1 or Trkbt2 Fail To Indumentioning

confidence: 99%

Signal Transduction Mediated by the Truncated trkB Receptor Isoforms, trkB.T1 and trkB.T2

Baxter¹,

et al. 1997

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The trkB family of transmembrane proteins serves as receptors for BDNF and NT-4/5. The family is composed of a tyrosine kinase-containing isoform as well as several alternatively spliced "truncated receptors" with identical extracellular ligandbinding domains but very small intracellular domains. The two best-characterized truncated trkB receptors, designated as trkB.T1 and trkB.T2, contain intracellular domains of only 23 and 21 amino acids, respectively. Although it is known that the tyrosine kinase isoform (trkB.FL) is capable of initiating BDNF and NT-4/5-induced signal transduction, the functional role or roles of the truncated receptors remain enigmatic. At the same time, the potential importance of the truncated receptors in the development, maintenance, and regeneration of the nervous system has been highlighted by recent developmental and injury paradigm investigations. Here we have used trkB cDNA transfected cell lines to demonstrate that both trkB.T1 and trkB.T2 are capable of mediating BDNF-induced signal transduction. More specifically, BDNF activation of either trkB.T1 or trkB.T2 increases the rate of acidic metabolite release from the cell, a common physiological consequence of many signaling pathways. Further, these trkB.T1-and trkB.T2-mediated changes occur with kinetics distinct from changes mediated by trkB.FL, suggesting the participation of at least some unique rate-limiting component or components. Mutational analysis demonstrates that the isoform-specific sequences within the intracellular domains of each receptor are essential for signaling capability. Finally, inhibitor studies suggest that kinases are likely to be involved in the trkB.T1 and trkB.T2 signaling pathways.

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Induction of ornithine decarboxylase by nerve growth factor dissociated from effects on survival and neurite outgrowth

Cited by 110 publications

References 19 publications

Structure of the gene encoding VGF, a nervous system-specific mRNA that is rapidly and selectively induced by nerve growth factor in PC12 cells.

Structure of the gene encoding VGF, a nervous system-specific mRNA that is rapidly and selectively induced by nerve growth factor in PC12 cells.

Direct transcriptional stimulation of the ornithine decarboxylase gene by Fos in PC12 cells but not in fibroblasts.

Signal Transduction Mediated by the Truncated trkB Receptor Isoforms, trkB.T1 and trkB.T2

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