Dual Specificity Phosphatase 5‐Substrate Interaction: A Mechanistic Perspective. Issue 4 (12th September 2017)

• Record Type: Journal Article
• Authors: Kutty, Raman G.; Talipov, Marat R.; Bongard, Robert D.; Lipinski, Rachel A. Jones; Sweeney, Noreena L.; Sem, Daniel S.; Rathore, Rajendra; Ramchandran, Ramani
• Is Part Of: Comprehensive physiology. Volume 7:Issue 4(2017)
• Page Start: 1449
• Page End: 1461
• Publication Date: 2017-09-12
• DOI: 10.1002/cphy.c170007
• Languages: English
• ISSNs: 2040-4603

Abstract

ABSTRACT: The mammalian genome contains approximately 200 phosphatases that are responsible for catalytically removing phosphate groups from proteins. In this review, we discuss dual specificity phosphatase 5 (DUSP5). DUSP5 belongs to the dual specificity phosphatase (DUSP) family, so named after the family members' abilities to remove phosphate groups from serine/threonine and tyrosine residues. We provide a comparison of DUSP5's structure to other DUSPs and, using molecular modeling studies, provide an explanation for DUSP5's mechanistic interaction and specificity toward phospho‐extracellular regulated kinase, its only known substrate. We also discuss new insights from molecular modeling studies that will influence our current thinking of mitogen‐activated protein kinase signaling. Finally, we discuss the lessons learned from identifying small molecules that target DUSP5, which might benefit targeting efforts for other phosphatases. © 2017 American Physiological Society. Compr Physiol 7:1449‐1461, 2017.