Direct activation of the serine/threonine kinase activity of raf-1 through tyrosine phosphorylation by the PDGF β-receptor

Morrison, Deborah K.; Kaplan, David R.; Escobedo, Jaime A.; Rapp, Ulf R.; Roberts, Thomas M.; Williams, Lewis T.

doi:10.1016/0092-8674(89)90100-1

Cited by 513 publications

(242 citation statements)

References 26 publications

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“…The dominant negative MEK1 mutant (MEK1S218/222A) (Pang et al, 1995) was provided by Dr A Saltiel (Parke Davis Pharmaceuticals, Ann Arbor, MI, USA), the wild-type and the kinase inactive SEK-1 mutant (SEK1 K 299 R) (Sanchez et al, 1994) were provided by Dr J Cherno (Fox Chase Cancer Center). Activated Raf1 (Raf1Y340D) and the dominant inhibitory Raf1 mutant (Raf1S621A) were provided by Dr D Morrison (Morrison et al, 1989) (NCI, FCRDC, Frederick, MD, USA). Finally, the calmodulin modulating ligand (CAML) expression plasmid (Bram and Crabtree, 1994) was provided by Dr R Bram (St. Jude's Children's Hospital, Memphis, TN, USA).…”

Section: Plasmidsmentioning

confidence: 99%

Tpl-2 induces IL-2 expression in T-cell lines by triggering multiple signaling pathways that activate NFAT and NF-κB

1998

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The Tpl-2 kinase activates the nuclear factor of activated T cells (NFAT) and induces IL-2 expression in T-cell lines. Here we show that the activation of the IL-2 promoter by Tpl-2 is inhibited by mutant signaling molecules that inhibit the mitogen-activated protein kinase (MAPK) or the calcineurin/NFAT pathways and is promoted by combinations of signaling molecules that activate these pathways. We, therefore, conclude that signals generated by the convergence of the MAPK and the calcineurin/NFAT pathway are necessary and su cient for the activation of the IL-2 promoter by Tpl-2. The activation of both the IL-2 promoter and an NFAT-driven minimal promoter were shown to depend on signals transduced by Raf1. However, it was only the IL-2 promoter whose activation by Tpl-2 was fully blocked by the dominant negative mutant MEK1S218/ 222A and the MEK1/MEK2 inhibitor PD098059. Since the activation of NFAT is MAPK-dependent these ®ndings suggested that the activation of MAPK by Tpl-2 is either independent or only partially dependent on MEK1 and MEK2. In addition, they suggested that the activation of the IL-2 promoter is under the control of not only NFAT but also a second factor whose activation is MEK-dependent. Experiments in COS-1 and EL-4 cells con®rmed both hypotheses and revealed that the second factor activated by Tpl-2 is NF-kB. While the activation of the IL-2 promoter and an NFAT-driven minimal promoter by Tpl-2 was fully blocked by the dominant negative mutant NFATD418, it was only partially blocked by the calcineurin inhibitor cyclosporin A suggesting that the Tpl-2-mediated NFAT activation is under the control of a combination of calcineurindependent and independent pathways. Both pathways were fully blocked by Bcl-2 or Bcl-X L .

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Section: Plasmidsmentioning

confidence: 99%

Tpl-2 induces IL-2 expression in T-cell lines by triggering multiple signaling pathways that activate NFAT and NF-κB

1998

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“…The molecular pathways controlling cell growth and death are deeply intertwined, with gene products as diverse as Myc (Evan et al, 1992;Harrington et al, 1994;Barone and Courtneidge, 1995;Packham et al, 1996;Kauffmann-Zeh et al, 1997), Raf (Morrison et al, 1989;Pumiglia and Decker, 1997;Woods et al, 1997) and MAP kinase (Traverse et al, 1992;Ben-Levy et al, 1994;Marshall, 1995;Marte et al, 1995;Kimura et al, 1999) being firmly implicated in both outcomes. By the same token, well-characterised mitogens such as the epidermal growth factor receptor (EGFR) and the ErbB2 (HER2/neu) oncoprotein have been causally linked to cell growth inhibition and apoptosis (Gill and Lazar, 1981;Kawamoto et al, 1984;Filmus et al, 1985;Polet, 1990;Tagliabue et al, 1991;Armstrong et al, 1994;Harris et al, 1995;Kita et al, 1996).…”

mentioning

confidence: 99%

Dominant negative knockout of p53 abolishes ErbB2-dependent apoptosis and permits growth acceleration in human breast cancer cells

et al. 2002

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We previously reported that the ErbB2 oncoprotein prolongs and amplifies growth factor signalling by impairing liganddependent downregulation of hetero-oligomerised epidermal growth factor receptors. Here we show that treatment of A431 cells with different epidermal growth factor receptor ligands can cause growth inhibition to an extent paralleling ErbB2 tyrosine phosphorylation. To determine whether such growth inhibition signifies an interaction between the cell cycle machinery and ErbB2-dependent alterations of cell signalling kinetics, we used MCF7 breast cancer cells (which express wild-type p53) to create transient and stable ErbB2 transfectants (MCF7-B2). Compared with parental cells, MCF7-B2 cells are characterised by upregulation of p53, p21 WAF and Myc, downregulation of Bcl2, and apoptosis. In contrast, MCF7-B2 cells co-transfected with dominant negative p53 (MCF7-B2/Dp53) exhibit reduced apoptosis and enhanced growth relative to both parental MCF7-B2 and control cells. These data imply that wild-type p53 limits survival of ErbB2-overexpressing breast cancer cells, and suggest that signals of varying length and/or intensity may evoke different cell outcomes depending upon the integrity of cell cycle control genes. We submit that acquisition of cell cycle control defects may play a permissive role in ErbB2 upregulation, and that the ErbB2 overexpression phenotype may in turn select for the survival of cells with p53 mutations or other tumour suppressor gene defects.

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“…The pBC12/lynA and pBC121lynB plasmids were then transfected into Cos-1 cells separately (4 (38), and the immunocomplexes were collected with protein A-agarose (Bethesda Research Laboratories) and analyzed by SDS-PAGE. Immunoprecipitates were also treated with calf intestinal alkaline phosphatase (Boehringer) and potato acid phosphatase (Boehringer) as described previously (22). In the in vitro kinase assay (27), PBS-washed cells were lysed in 2% Nonidet P-40 and TEN (50 mM Tris-HCl [pH 7.4], 1 mM EDTA, 0.15 M NaCl).…”

mentioning

confidence: 99%

Hematopoietic cells express two forms of lyn kinase differing by 21 amino acids in the amino terminus.

Yi¹,

Bolen²,

Ihle³

1991

Mol. Cell. Biol.

146

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Direct activation of the serine/threonine kinase activity of raf-1 through tyrosine phosphorylation by the PDGF β-receptor

Cited by 513 publications

References 26 publications

Tpl-2 induces IL-2 expression in T-cell lines by triggering multiple signaling pathways that activate NFAT and NF-κB

Tpl-2 induces IL-2 expression in T-cell lines by triggering multiple signaling pathways that activate NFAT and NF-κB

Dominant negative knockout of p53 abolishes ErbB2-dependent apoptosis and permits growth acceleration in human breast cancer cells

Hematopoietic cells express two forms of lyn kinase differing by 21 amino acids in the amino terminus.

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