Transforming gene product of Rous sarcoma virus phosphorylates tyrosine

Hunter, Tony; Sefton, Bartholomew M.

doi:10.1073/pnas.77.3.1311

Cited by 2,157 publications

(1,224 citation statements)

References 32 publications

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“…MK-801 is a potent and selective antagonist of the NMDA type of glutamate receptors which bind to the ion channel of the receptor complex [4,5]. To further confirm that the protective effect of MK-801 is mediated by its action on the NMDA type of glutamate receptors, we assessed the effect of another specific antagonist, AP-5, which acts on a dif'ferent site (the glutamate binding site) of the same receptor.…”

Section: Resultsmentioning

confidence: 99%

Acute ammonia toxicity is mediated by the NMDA type of glutamate receptors

et al. 1992

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Previous experiments in our luboratory suggested that ammonium toxici1y could be medialed by the NMDA 1ype of glutamate receptors. To assess this hypothesis we tcstcd if MK-501. a specific antagonist of the NMDA receptor, is able to prevent ammonium toxicity. Mice and ra1s were injected i.p. with 12 and 7 mmol/kg of ammonium acetalc. rcspL%tively. 73% of the mice and 70% of the ruts died. However. when the animals were injected i.p. with 2 mg/kg of MK-501. I5 min before ammonium injection, only 5% of 1hc mice and 15% of 1hc rats died. The remarkable protection afforded by MK-SOi indicates (ha1 ammonia toxici1y is mediated by the NMDA receptor.Ammonia 1oxicity; NMDA reccplor; MK-901; Hyperammoncmia

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Section: Resultsmentioning

confidence: 99%

Acute ammonia toxicity is mediated by the NMDA type of glutamate receptors

et al. 1992

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“…This is supported by our ®nding of low levels of both GFAP and v-src RNA also in Schwann cells of peripheral nerves, which were probably the source of the signals detected in extracerebral tissues by RT ± PCR (JPS, JW and AA, unpublished data). The transforming activity of the viral Src oncoprotein (Collett and Erikson, 1978) is dependent on its kinase activity and hence on its ability to phosphorylate speci®c cellular proteins at tyrosine residues (Hunter and Sefton, 1980). The absence of a pathological phenotype in line src3 can be explained by the observation of a truncated v-src.…”

Section: Discussionmentioning

confidence: 99%

Development and malignant progression of astrocytomas in GFAP-v-src transgenic mice

et al. 1997

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We have generated a transgenic mouse model for astrocytoma by expressing the v-src kinase under control of the glial ®brillary acidic protein (GFAP) gene regulatory elements in astrocytes. Abnormal astrogliosis was observed in all transgenic animals already at 2 weeks postnatally, frequently followed by the development of dysplastic changes. Later, small proliferative foci arose, and overt astrocytoma developed in the brain and spinal cord in 14.4% of mice after a follow up time of 65 weeks. While early lesions were histologically consistent with low-grade astrocytoma, at later stages most tumors were highly mitotic and frankly malignant. Vascular endothelial growth factor (VEGF) was expressed by tumor cells already at early stages, suggesting induction by v-src, and it was most pronounced in pseudopalisading cells surrounding necrotic areas, implying additional upregulation by hypoxia. In larger lesions, mitotic activity and expression of¯k-1, the cognate receptor of VEGF were induced in endothelial cells. Therefore, end-stage tumors mimicked the morphological and molecular characteristics of human glioblastoma multiforme. Time course and stochastic nature of the process indicate that v-src did not su ce for malignant transformation, and that astrocytomas were the result of a multistep process necessitating co-operation of additional genetic events.

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“…Aliquots of the anti-JAK2 immunoprecipitated material were then subjected to in vitro radiolabelling autokinase assays, which provide a basic measure of JAK2's enzymatic activity [33][34][35]. No detectable activity was associated with the kinaseinactive EGFP/rJAK2(K882E), as anticipated.…”

Section: Characteristics Of the Egfp/rjak2 Chimeras Produced In Cos-7mentioning

confidence: 99%

Kinase activity and subcellular distribution of a chimeric green fluorescent protein-tagged Janus kinase 2

Lee¹,

Duhé²

2006

J Biomed Sci

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SummaryJanus kinase 2 (JAK2) is an essential intracellular signal transducer for numerous cytokines and hormones. To examine how JAK2 structural modifications can affect cellular physiology, we created expression vectors for chimeric proteins containing an enhanced green fluorescent protein (EGFP) fused to rat JAK2 (EGFP/rJAK2), and a kinase-inactive variant, EGFP/rJAK2(K882E). The properties of EGFP/rJAK2 were examined following transient transfection of COS-7 cells. EGFP/rJAK2 was expressed throughout the cell, and was found in subcellular membrane, cytosolic and nuclear fractions. Interestingly, EGFP/rJAK2 phosphorylated other proteins in situ without additional cytokine stimulation. Furthermore, despite a much higher level of tyrosine phosphorylation arising from in situ autophosphorylation, the in vitro radiolabelling autokinase activity of EGFP/rJAK2 was significantly less than that of the endogenous JAK2. These results reveal a technical limitation of the application of the ''conventional'' in vitro radiolabelling autokinase assay to hyperphosphorylated forms of the enzyme and illustrate the potential weaknesses in individual assays commonly used to determine JAK2's enzymatic activity and subcellular distribution. We also suggest that the EGFP/rJAK2 model can be very useful in studying JAK2-related cancers, because its ubiquitous distribution and abnormal constitutive hyperphosphorylation may distinguish it from the cytokine-regulated, membrane-proximal form of JAK2 associated with normal physiology.

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Transforming gene product of Rous sarcoma virus phosphorylates tyrosine

Cited by 2,157 publications

References 32 publications

Acute ammonia toxicity is mediated by the NMDA type of glutamate receptors

Acute ammonia toxicity is mediated by the NMDA type of glutamate receptors

Development and malignant progression of astrocytomas in GFAP-v-src transgenic mice

Kinase activity and subcellular distribution of a chimeric green fluorescent protein-tagged Janus kinase 2

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