Title:Targeting Kinase Interaction Networks: A New Paradigm in PPI Based Design of Kinase Inhibitors
VOLUME: 19 ISSUE: 6
Author(s):Pranitha Jenardhanan, Manivel Panneerselvam and Premendu P. Mathur*
Affiliation:Centre for Bioinformatics, Pondicherry University, Puducherry, Department of Biotechnology, BJM School of Biosciences, Indian Institute of Technology Madras, Chennai, Department of Biochemistry & Molecular Biology, School of Life Sciences, Pondicherry University, Puducherry
Keywords:Human kinome, Kinases, Protein-protein interactions (PPI), Peptide inhibitors, Peptidomimetics, Kinase interaction
network.
Abstract:
Background: Kinases are key modulators in regulating diverse range of cellular activities
and are an essential part of the protein-protein interactome. Understanding the interaction of kinases
with different substrates and other proteins is vital to decode the cell signaling machinery as well as
causative mechanism for disease onset and progression.
Objective: The objective of this review is to present all studies on the structure and function of few
important kinases and highlight the protein-protein interaction (PPI) mechanism of kinases and the
kinase specific interactome databases and how such studies could be utilized to develop anticancer
drugs.
Methods: The article is a review of the detailed description of the various domains in kinases that are
involved in protein-protein interactions and specific inhibitors developed targeting these PPI domains.
Results: The review has surfaced in depth the interacting domains in key kinases and their features
and the roles of PPI in the human kinome and the various signaling cascades that are involved in certain
types of cancer.
Conclusion: The insight availed into the mechanism of existing peptide inhibitors and peptidomimetics
against kinases will pave way for the design and generation of domain specific peptide inhibitors
with better productivity and efficiency and the various software and servers available can be of great
use for the identification and analysis of protein-protein interactions.