Iavarone, Carlo (2006) JNK and ERK8 as downstream effectors of receptor tyrosine kinases. [Tesi di dottorato] (Unpublished)


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Item Type: Tesi di dottorato
Resource language: English
Title: JNK and ERK8 as downstream effectors of receptor tyrosine kinases
Iavarone, CarloUNSPECIFIED
Date: 2006
Date type: Publication
Number of Pages: 69
Institution: Università degli Studi di Napoli Federico II
Department: Biologia e patologia cellullare e molecolare "L. Califano"
Dottorato: Patologia e fisiopatologia molecolare
Ciclo di dottorato: 17
Coordinatore del Corso di dottorato:
Avvedimento, Vittorio EnricoUNSPECIFIED
Formisano, SilvestroUNSPECIFIED
Date: 2006
Number of Pages: 69
Keywords: Mitogen Activated Protein Kinase (MAPK), Receptor Tyrosine Kinase (RTK), Transcription factor
Settori scientifico-disciplinari del MIUR: Area 06 - Scienze mediche > MED/13 - Endocrinologia
Area 06 - Scienze mediche > MED/05 - Patologia clinica
Area 05 - Scienze biologiche > BIO/13 - Biologia applicata
Area 06 - Scienze mediche > MED/09 - Medicina interna
Area 06 - Scienze mediche > MED/04 - Patologia generale
Date Deposited: 01 Aug 2008
Last Modified: 05 Dec 2014 11:43
URI: http://www.fedoa.unina.it/id/eprint/784
DOI: 10.6092/UNINA/FEDOA/784

Collection description

MAP kinases are a super-family of serine-threonine protein kinases expressed in all eukaryotic cells. In mammals, there are many MAP kinases with different biological functions, grouped in distinctly regulated groups, ERK1/2 (extracellular signal related kinase, ERK), JNKs (jun amino terminal kinase, JNK), p38 and “atypical” MAP kinases. The MAP kinase transduction system is particularly important in growth factors signaling, which in turn control cell growth, proliferation, differentiation, survival and migration by activating receptor tyrosine kinase (RTK) family members, as platelet-derived growth factor (PDGF) and RET. In the first report, we show that JNK is required for PDGF induction of c-myc expression. Furthermore, we identify a phylogenetically conserved AP-1 responsive element in the human, mouse and even drosophila c-myc promoter. Such element binds, in vivo, to members of the Jun family of transcription factors, c-Jun and JunD, as indicated by chromatin immunoprecipitation analysis. Finally, we show that, through this element, PDGF is able to control the activity of the c-myc transcription factor promoter in an AP-1 dependent fashion, implying the existence of a novel signaling pathway linking the PDGF receptor, through JNK and Jun proteins, to nuclear events culminating in the expression of the c-myc proto-oncogene. In the second report, we show that RET/PTC3 activates Erk8, a new member of “atypical” MAP kinases group, by an Abl-dependent but Src-independent mechanism and demonstrate a key role for Tyr981 of RET/PTC3 in the initiation of such signaling pathway. Also, by using an alternative Erk8 splice variant, Erk8, lacking the C-terminal domain, we establish a role for this region in the activation of this MAP kinase by RET/PTC3. Finally, the use of a dominant interfering molecule for Erk8 revealed that RET/PTC3 requires this MAP kinase to stimulate the c-jun transcription factor promoter.


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