Characterisation of the role of human Evolutionary Conserved Signalling Intermediate in Toll (ECSIT) in Mitogen Activated Protein Kinase (MAPK) signalling

Evolutionarily conserved signalling intermediate in Toll pathways (ECSIT) was identified orginally as a TNF receptor associated factor 6 (TRAF6) interacting partner. The murine homolog mECSIT has been shown to be involved in NFκB, MAPK, BMP and mitochondrial signalling. To date there is no work published on the human homolog, hECSIT. In this thesis, I present data indicating that hECSIT is involved in NFκB, BMP and MAPK signalling. There is a striking difference in the role of hECSIT and mECSIT in the activation of inflammatory transcription factors NFκB, ELK-1 and AP-1; with mECSIT augmenting their activation and hECSIT having an inhibitory role. In addition I demonstrate that hECSIT specifically targets the p42/44 branch of MAPK signalling. Suppression of endogenous hECSIT results in increased basal and proinflammatory induced phosphorylation of p42/44 but not JNK or p38. Thus, hECSIT signalling represents a novel means of regulating p42/44 and its downstream targets.

Level dc:type.qualificationlevel

masters

Grantor dc:publisher.institution

National University of Ireland Maynooth

Year dc:date.issued

2012

Author dc:creator

• Kirwan, Annie

• Institute of Immunology

Language dc:language

en