Journal of Proteomics & Bioinformatics
Open Access

Protein interaction networks regulating cell signaling in cancer

2^nd International Conference on Proteomics & Bioinformatics

July 2-4, 2012 Embassy Suites Las Vegas, USA

HIgor Stagljar

Accepted Abstracts: J Proteomics Bioinform

Abstract :

Receptor Tyrosine Kinases (RTKs) are cell surface receptors that represent central components of cell signaling networks. Of the 90 unique tyrosine kinase genes identified in the human genome, 58 encode RTK proteins. RTKs have been shown not only to be key regulators of normal cellular processes, but also to have a critical role in the development and progression of many types of cancers. Nevertheless, there is a lack of in-depth understanding of RTK networks because of their complex biochemical features, enormous complexity and multiplicity. This is a major obstacle for designing improved and more targeted therapies, and importantly, understanding the biology of receptor deregulation, leading to cancerogenesis. The application of interactive proteomics is a promising approach for improving our understanding of RTK networks, however, it requires developing sophisticated PPI technologies to probe interactomes of the full-length human RTKs in a high-throughput format (1). We previously developed one such technology for the in vivo detection of membrane protein interactions called the membrane two-hybrid (MYTH) system (2-5). Furthermore, we have recently modified the original MYTH system to make it amenable for screening of PPIs of the full-length human RTKs such as the human Epidermal Growth Factor Receptor (EGFR) and identified Histone Deacetylase 6 (HDAC6) as a negative regulator of the EGFR endocytosis (6). We are currently using a modified MYTH, coupled to bioinformatics, to derive a complete map of PPIs linked to all remaining 57 human RTKs. During my talk, I will discuss exciting new findings indicating that the newly identified RTK-interacting proteins play novel roles in regulating the activity of these integral membrane proteins in vivo and in vitro. Our systematic approach offers an unbiased systems level view that may identify novel drug targets and contribute to therapeutic research.