New Perspectives, Opportunities, and Challenges in Exploring the Human Protein Kinome



Wilson, Leah J, Linley, Adam ORCID: 0000-0002-8176-5560, Hammond, Dean E ORCID: 0000-0002-6326-8739, Hood, Fiona E, Coulson, Judy M ORCID: 0000-0003-2191-2001, MacEwan, David J ORCID: 0000-0002-2879-0935, Ross, Sarah J, Slupsky, Joseph R ORCID: 0000-0002-7410-9004, Smith, Paul D, Eyers, Patrick A ORCID: 0000-0002-9220-2966
et al (show 1 more authors) (2018) New Perspectives, Opportunities, and Challenges in Exploring the Human Protein Kinome. CANCER RESEARCH, 78 (1). pp. 15-29.

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Abstract

The human protein kinome comprises 535 proteins that, with the exception of approximately 50 pseudokinases, control intracellular signaling networks by catalyzing the phosphorylation of multiple protein substrates. While a major research focus of the last 30 years has been cancer-associated Tyr and Ser/Thr kinases, over 85% of the kinome has been identified to be dysregulated in at least one disease or developmental disorder. Despite this remarkable statistic, for the majority of protein kinases and pseudokinases, there are currently no inhibitors progressing toward the clinic, and in most cases, details of their physiologic and pathologic mechanisms remain at least partially obscure. By curating and annotating data from the literature and major public databases of phosphorylation sites, kinases, and disease associations, we generate an unbiased resource that highlights areas of unmet need within the kinome. We discuss strategies and challenges associated with characterizing catalytic and noncatalytic outputs in cells, and describe successes and new frontiers that will support more comprehensive cancer-targeting and therapeutic evaluation in the future. <i>Cancer Res; 78(1); 15-29. ©2017 AACR</i>.

Item Type: Article
Uncontrolled Keywords: Humans, Protein Kinases, Protein Kinase Inhibitors, Phosphorylation, Mutation
Depositing User: Symplectic Admin
Date Deposited: 15 Jan 2018 11:43
Last Modified: 13 Feb 2024 14:34
DOI: 10.1158/0008-5472.CAN-17-2291
Related URLs:
URI: https://livrepository.liverpool.ac.uk/id/eprint/3016125