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Title: Regulation of the RAS-ERK pathway by SHOC2
Author: Young, L. C.
ISNI:       0000 0004 8497 6384
Awarding Body: UCL (University College London)
Current Institution: University College London (University of London)
Date of Award: 2016
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SHOC2 is mutated in Noonan syndrome and plays a key role in the activation of the RAS-ERK pathway, which is upregulated in the majority of human cancers. SHOC2 functions as a PP1 regulatory protein and as an effector of MRAS. SHOC2 and MRAS form a complex with SCRIB, a polarity protein with tumour suppressor properties. SCRIB functions as a PP1 regulatory protein and a model is proposed whereby SCRIB inhibits the ERK pathway by antagonising SHOC2 complex-mediated RAF dephosphorylation through a mechanism which is dependent on the SCRIB-PP1 interaction. SHOC2 complex function is required for EGF-stimulated RAF dimerisation and is selectively required for the malignant properties of tumour cells with mutant RAS. MRAS and SHOC2 also play a key role in polarised migration and I propose that MRAS, through its ability to recruit a complex with paradoxical components, coordinates ERK pathway dynamics with polarity. The SHOC2-MRAS-PP1 complex plays a key role during tumourigenic growth and is an attractive target for pharmacological inhibition in malignancies with upregulated RAS-ERK pathway activity.
Supervisor: Rodriguez-Viciana, P. Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available