Dual Specificity Phosphatase 5‐Substrate Interaction: A Mechanistic Perspective

Authors

Raman G. Kutty, Medical College of Wisconsin
Marat R. Talipov, New Mexico State UniversityFollow
Robert D. Bongard, Medical College of Wisconsin
Rachel A. Jones Lipinski, Medical College of WisconsinFollow
Noreena Sweeney, Concordia University of Wisconsin
Daniel Sem, Marquette UniversityFollow
Rajendra Rathore, Marquette University
Ramani Ramchandran, Medical College of Wisconsin

Document Type

Article

Language

eng

Publication Date

2017

Publisher

American Physiological Society

Source Publication

Comprehensive Physiology

Source ISSN

2040-4603

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.

Comments

Comprehensive Physiology, Vol. 7 (2017): 1447-1461. DOI.

Recommended Citation

Kutty, Raman G.; Talipov, Marat R.; Bongard, Robert D.; Jones Lipinski, Rachel A.; Sweeney, Noreena; Sem, Daniel; Rathore, Rajendra; and Ramchandran, Ramani, "Dual Specificity Phosphatase 5‐Substrate Interaction: A Mechanistic Perspective" (2017). Chemistry Faculty Research and Publications. 885.
https://epublications.marquette.edu/chem_fac/885