Induction of c-fos gene and protein by growth factors precedes activation of c-myc

Müller, Rolf; Bravo, Rodrigo; Burckhardt, Johann Jakob; Curran, Tom

doi:10.1038/312716a0

Cited by 1,352 publications

(624 citation statements)

References 26 publications

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“…Rats were deeply anesthetized with sodium pentobarbital (0.2 g/kg) 75 min after microinjection, since translation of c-fos mRNA to Fos protein is maximal between 60 and 120 min (Muller et al, 1984). After transcardial perfusion, brains were removed and placed in 4% paraformaldehyde for 2 h, 30% sucrose overnight, and then sectioned at 40 mm and stored in 0.2 M NaPb, pH 7.4.…”

Section: Fos-like Protein Immunohistochemistrymentioning

confidence: 99%

Endocannabinoid Hedonic Hotspot for Sensory Pleasure: Anandamide in Nucleus Accumbens Shell Enhances ‘Liking’ of a Sweet Reward

Mahler

Smith

Berridge

2007

Neuropsychopharmacol

303

258

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Cannabinoid drugs such as D 9 -THC are euphoric and rewarding, and also stimulate food intake in humans and animals. Little is known about how naturally occurring endogenous brain cannabinoids mediate pleasure from food or other natural sensory rewards. The taste reactivity paradigm measures effects of brain manipulations on affective orofacial reactions to intraorally administered pleasant and unpleasant tastes. Here we tested if anandamide microinjection into medial nucleus accumbens shell enhances these affective reactions to sweet and bitter tastes in rats. Anandamide doubled the number of positive 'liking' reactions elicited by intraoral sucrose, without altering negative 'disliking' reactions to bitter quinine. Anandamide microinjections produced Fos plumes of approximately 0.02-1 mm 3 volume. Plume-based maps, integrated with behavioral data, identified the medial shell of accumbens as the anatomical hotspot responsible for hedonic amplification. Anandamide produced especially intense hedonic enhancement in a roughly 1.6 mm 3 'hedonic hotspot' in dorsal medial shell, where anandamide also stimulated eating behavior. These results demonstrate that endocannabinoid signals within medial accumbens shell specifically amplify the positive hedonic impact of a natural reward (though identification of the receptor specificity of this effect will require future studies). Identification of an endocannabinoid hotspot for sensory pleasure gives insight into brain mechanisms of natural reward, and may be relevant to understanding the neural effects of cannabinoid drugs of abuse and therapeutic agents.

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Section: Fos-like Protein Immunohistochemistrymentioning

confidence: 99%

Endocannabinoid Hedonic Hotspot for Sensory Pleasure: Anandamide in Nucleus Accumbens Shell Enhances ‘Liking’ of a Sweet Reward

Mahler

Smith

Berridge

2007

Neuropsychopharmacol

303

258

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“…However, in these experiments the strength of the Raf signal as well as the expression of the p21 cip1 protein have not been analysed. The expression of the c-myc gene is induced early after growth factor stimulation of arrested cells (MuÈ ller et al, 1984). The gene is expressed throughout the whole cell cycle (Waters et al, 1991).…”

Section: Constitutive Activation Of Ras or Raf Induces Cyclin D1 Overmentioning

confidence: 99%

Cell cycle targets of Ras/Raf signalling

1998

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The regulation of cell proliferation in multicellular organisms is a complex process, which is primarily regu-lated by external growth factors provided by surrounding cells. Once induced to proliferate, the passage through the mitotic cell cycle is directed by the components of the so called cell cycle machinery. Over the last years research on growth factor signaltransduction and the components of the cell cycle system has lead to a detailed knowledge of the mechanisms by which growth factors transmit their signals and of the relationship between the components of the cell cycle machinery. The remaining question how the growth factor mediated signal-transduction cascades couple with the cell cycle regulators has recently been a focus of interest.Keywords: Ras; Raf; cell cycleThe Ras GTP-binding protein and Raf kinases have a central role in transmitting growth factor-triggered signals. The Ras protein is an important e ector of growth factor receptors and activates di erent signaltransduction cascades (Daum et al., 1994;Avruch et al., 1994;Rodriguez Viciana et al., 1996;Symons, 1996). One of these is the Ras/Raf/Mek/Erk cascade (Daum et al., 1994). By direct interaction the Ras protein targets the Raf kinase to the plasma membrane where the catalytic activity of the kinase becomes activated. Subsequently Raf stimulates the Mek kinase by phosphorylation, which then phosphorylates and activates the Erk kinases. The Erk kinases shuttle into the nucleus and induce the activity of transcription factors. By employing constitutively active and dominant negative mutants of the Ras and Raf proteins it has been shown that the Ras/Raf signaltransduction cascade plays a crucial role in the regulation of cell proliferation by growth factors (Mulcahy et al

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“…The AP-1 complex Activation of the AP-1 transcription factor complex is a universal response of a wide variety of mammalian cells to a broad range of external stimuli, including growth factors, chemokines and ECM (Muller et al, 1984;Verma and Sassone-Corsi, 1987). AP-1 is a dimeric transcription factor that consists of members of the Fos and Jun gene families, including FOS, FOSB, FOSL1 (Fra-1), FOSL2 (Fra-2), JUN, JUNB and JUND (Curran and Franza, 1988) that bind to variations of the consensus DNA binding site TGAg/cTCA, usually located in the promoter region of target genes (Figure 1).…”

Section: Introductionmentioning

confidence: 99%