Comparative protein interaction network analysis identifies shared and distinct functions for the human ROCO proteins

Tomkins, J. E., Dihanich, S., Beilina, A., Ferrari, R., Ilacqua, N., Cookson, M. R., Lewis, P. A. and Manzoni, C. (2018) Comparative protein interaction network analysis identifies shared and distinct functions for the human ROCO proteins. Proteomics, 18 (10). 1700444. ISSN 1615-9853 doi: 10.1002/pmic.201700444

Abstract/Summary

Signal transduction cascades governed by kinases and GTPases are a critical component of the command and control of cellular processes, with the precise outcome partly determined by direct protein‐protein interactions (PPIs). Here, we use the human ROCO proteins as a model for investigating PPI signalling events – taking advantage of the unique dual kinase/GTPase activities and scaffolding properties of these multidomain proteins. We report PPI networks that encompasses the human ROCO proteins, developed using two complementary approaches. First, using our recently developed weighted PPI network analysis (WPPINA) pipeline, a confidence‐weighted overview of validated ROCO protein interactors was obtained from peer‐reviewed literature. Second, novel ROCO PPIs were assessed experimentally via protein microarray screens. We compared the networks derived from these orthologous approaches to identify common elements within the ROCO protein interactome; functional enrichment analysis of this common core of the network identified stress response and cell projection organisation as shared functions within this protein family. Despite the presence of these commonalities, our results suggest that many unique interactors and therefore some specialised cellular roles have evolved for different members of the ROCO proteins. Overall, this multi‐approach strategy to increase the resolution of protein interaction networks represents a prototype for the utility of PPI data integration in understanding signalling biology.

Item Type	Article
URI	https://reading-clone.eprints-hosting.org/id/eprint/76656
Identification Number/DOI	10.1002/pmic.201700444
Refereed	Yes
Divisions	Life Sciences > School of Chemistry, Food and Pharmacy > School of Pharmacy > Division of Pharmacology
Uncontrolled Keywords	LRRK2, LRRK1, DAPK1, MASL1/MAFHAS1, ROCO proteins, protein microarray, protein network
Publisher	Wiley
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