JOSE RAMIREZ | Instituto Tecnológico de Matamoros (original) (raw)

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Papers by JOSE RAMIREZ

Research paper thumbnail of Rapid Phosphorylation of Ets-2 Accompanies Mitogen-Activated Protein Kinase Activation and the Induction of Heparin-Binding Epidermal Growth Factor Gene …

… and cellular biology, 1997

Heparin-binding epidermal growth factor (HB-EGF) gene transcription is rapidly activated in NIH 3... more Heparin-binding epidermal growth factor (HB-EGF) gene transcription is rapidly activated in NIH 3T3 cells transformed by oncogenic Ras and Raf and mediates the autocrine activation of the c-Jun N-terminal kinases (JNKs) observed in these cells. A 1.7-kb fragment of the promoter of the murine HB-EGF gene linked to a luciferase reporter was strongly induced following activation of ⌬Raf-1:ER, a conditionally active form of oncogenic human Raf-1. Promoter activation by ⌬Raf-1:ER required a composite AP-1/Ets transcription factor binding site located between bp ؊974 and ؊988 upstream of the translation initiation site. In vivo genomic footprinting indicated that the basal level of occupancy of this composite AP-1/Ets element increased following ⌬Raf-1:ER activation. Cotransfection of Ets-2 and p44 mitogen-activated protein (MAP) kinase expression vectors strongly potentiated HB-EGF promoter activation in response to ⌬Raf-1:ER. Potentiated activation required both p44 MAP kinase catalytic activity and threonine 72 in the Pointed domain of Ets-2. Biochemical assays demonstrated the ability of the p42 and p44 MAP kinases to phosphorylate Ets-2 on threonine 72. Importantly, in intact cells, the kinetics of phosphorylation of Ets-2 on this residue closely mirror the activation of the p42 and p44 MAP kinases and the observed onset of HB-EGF gene transcription following ⌬Raf-1:ER activation. These data firmly establish Ets-2 as a direct target of the Raf-MEK-MAP kinase signaling pathway and strongly implicate Ets-2 in the regulation of HB-EGF gene expression.

Research paper thumbnail of Rapid Phosphorylation of Ets-2 Accompanies Mitogen-Activated Protein Kinase Activation and the Induction of Heparin-Binding Epidermal Growth Factor Gene …

… and cellular biology, 1997

Heparin-binding epidermal growth factor (HB-EGF) gene transcription is rapidly activated in NIH 3... more Heparin-binding epidermal growth factor (HB-EGF) gene transcription is rapidly activated in NIH 3T3 cells transformed by oncogenic Ras and Raf and mediates the autocrine activation of the c-Jun N-terminal kinases (JNKs) observed in these cells. A 1.7-kb fragment of the promoter of the murine HB-EGF gene linked to a luciferase reporter was strongly induced following activation of ⌬Raf-1:ER, a conditionally active form of oncogenic human Raf-1. Promoter activation by ⌬Raf-1:ER required a composite AP-1/Ets transcription factor binding site located between bp ؊974 and ؊988 upstream of the translation initiation site. In vivo genomic footprinting indicated that the basal level of occupancy of this composite AP-1/Ets element increased following ⌬Raf-1:ER activation. Cotransfection of Ets-2 and p44 mitogen-activated protein (MAP) kinase expression vectors strongly potentiated HB-EGF promoter activation in response to ⌬Raf-1:ER. Potentiated activation required both p44 MAP kinase catalytic activity and threonine 72 in the Pointed domain of Ets-2. Biochemical assays demonstrated the ability of the p42 and p44 MAP kinases to phosphorylate Ets-2 on threonine 72. Importantly, in intact cells, the kinetics of phosphorylation of Ets-2 on this residue closely mirror the activation of the p42 and p44 MAP kinases and the observed onset of HB-EGF gene transcription following ⌬Raf-1:ER activation. These data firmly establish Ets-2 as a direct target of the Raf-MEK-MAP kinase signaling pathway and strongly implicate Ets-2 in the regulation of HB-EGF gene expression.

Research paper thumbnail of Rapid Phosphorylation of Ets-2 Accompanies Mitogen-Activated Protein Kinase Activation and the Induction of Heparin-Binding Epidermal Growth Factor Gene …

… and cellular biology, 1997

Heparin-binding epidermal growth factor (HB-EGF) gene transcription is rapidly activated in NIH 3... more Heparin-binding epidermal growth factor (HB-EGF) gene transcription is rapidly activated in NIH 3T3 cells transformed by oncogenic Ras and Raf and mediates the autocrine activation of the c-Jun N-terminal kinases (JNKs) observed in these cells. A 1.7-kb fragment of the promoter of the murine HB-EGF gene linked to a luciferase reporter was strongly induced following activation of ⌬Raf-1:ER, a conditionally active form of oncogenic human Raf-1. Promoter activation by ⌬Raf-1:ER required a composite AP-1/Ets transcription factor binding site located between bp ؊974 and ؊988 upstream of the translation initiation site. In vivo genomic footprinting indicated that the basal level of occupancy of this composite AP-1/Ets element increased following ⌬Raf-1:ER activation. Cotransfection of Ets-2 and p44 mitogen-activated protein (MAP) kinase expression vectors strongly potentiated HB-EGF promoter activation in response to ⌬Raf-1:ER. Potentiated activation required both p44 MAP kinase catalytic activity and threonine 72 in the Pointed domain of Ets-2. Biochemical assays demonstrated the ability of the p42 and p44 MAP kinases to phosphorylate Ets-2 on threonine 72. Importantly, in intact cells, the kinetics of phosphorylation of Ets-2 on this residue closely mirror the activation of the p42 and p44 MAP kinases and the observed onset of HB-EGF gene transcription following ⌬Raf-1:ER activation. These data firmly establish Ets-2 as a direct target of the Raf-MEK-MAP kinase signaling pathway and strongly implicate Ets-2 in the regulation of HB-EGF gene expression.

Research paper thumbnail of Rapid Phosphorylation of Ets-2 Accompanies Mitogen-Activated Protein Kinase Activation and the Induction of Heparin-Binding Epidermal Growth Factor Gene …

… and cellular biology, 1997

Heparin-binding epidermal growth factor (HB-EGF) gene transcription is rapidly activated in NIH 3... more Heparin-binding epidermal growth factor (HB-EGF) gene transcription is rapidly activated in NIH 3T3 cells transformed by oncogenic Ras and Raf and mediates the autocrine activation of the c-Jun N-terminal kinases (JNKs) observed in these cells. A 1.7-kb fragment of the promoter of the murine HB-EGF gene linked to a luciferase reporter was strongly induced following activation of ⌬Raf-1:ER, a conditionally active form of oncogenic human Raf-1. Promoter activation by ⌬Raf-1:ER required a composite AP-1/Ets transcription factor binding site located between bp ؊974 and ؊988 upstream of the translation initiation site. In vivo genomic footprinting indicated that the basal level of occupancy of this composite AP-1/Ets element increased following ⌬Raf-1:ER activation. Cotransfection of Ets-2 and p44 mitogen-activated protein (MAP) kinase expression vectors strongly potentiated HB-EGF promoter activation in response to ⌬Raf-1:ER. Potentiated activation required both p44 MAP kinase catalytic activity and threonine 72 in the Pointed domain of Ets-2. Biochemical assays demonstrated the ability of the p42 and p44 MAP kinases to phosphorylate Ets-2 on threonine 72. Importantly, in intact cells, the kinetics of phosphorylation of Ets-2 on this residue closely mirror the activation of the p42 and p44 MAP kinases and the observed onset of HB-EGF gene transcription following ⌬Raf-1:ER activation. These data firmly establish Ets-2 as a direct target of the Raf-MEK-MAP kinase signaling pathway and strongly implicate Ets-2 in the regulation of HB-EGF gene expression.

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