Targeting an oncogenic kinase/phosphatase signaling network for cancer therapy.
10.1016/j.apsb.2018.05.007
- Author:
Xiao-Mei QI
1
;
Fang WANG
1
;
Matthew MORTENSEN
1
;
Ryan WERTZ
1
;
Guan CHEN
1
Author Information
1. Department of Pharmacology and Toxicology, Medical College of Wisconsin, Milwaukee, WI 53226, USA.
- Publication Type:Journal Article
- Keywords:
Cancer development and progression;
Kinase/phosphatase signaling network;
PDZ-coupled protein-protein complex;
Phosphorylation and dephosphorylation;
Targeted cancer therapy
- From:
Acta Pharmaceutica Sinica B
2018;8(4):511-517
- CountryChina
- Language:English
-
Abstract:
Protein kinases and phosphatases signal by phosphorylation and dephosphorylation to precisely control the activities of their individual and common substrates for a coordinated cellular outcome. In many situations, a kinase/phosphatase complex signals dynamically in time and space through their reciprocal regulations and their cooperative actions on a substrate. This complex may be essential for malignant transformation and progression and can therefore be considered as a target for therapeutic intervention. p38 is a unique MAPK family member that contains a PDZ motif at its C-terminus and interacts with a PDZ domain-containing protein tyrosine phosphatase PTPH1. This PDZ-coupled binding is required for both PTPH1 dephosphorylation and inactivation of p38 and for p38 phosphorylation and activation of PTPH1. Moreover, the p38/PTPH1 complex can further regulate their substrates phosphorylation and dephosphorylation, which impacts Ras transformation, malignant growth and progression, and therapeutic response. This review will use the p38/PTPH1 signaling network as an example to discuss the potential of targeting the kinase/phosphatase signaling complex for development of novel targeted cancer therapy.
