Chapter I. Pathogenesis
Rev Diabet Stud,
2012,
9(4):188-200 |
DOI 10.1900/RDS.2012.9.188 |
Protein Tyrosine Phosphatases and Type 1 Diabetes: Genetic and Functional Implications of PTPN2 and PTPN22
Karen Cerosaletti, Jane H. Buckner
Translational Research Program, Benaroya Research Institute at Virginia Mason, Seattle, WA 98101, USA
Address correspondence to: Jane H. Buckner, Associate Director, Benaroya Research Institute, Director, Translational Research, Benaroya Research Institute at Virginia Mason, 1201 9th Ave, Seattle, WA 98101, USA, e-mail jbuckner@benaroyaresearch.org
Manuscript submitted December 16, 2012; resubmitted January 28, 2013; accepted January 29, 2013.
Keywords: type 1 diabetes, genome-wide association study, PTPN22, PTPN2, LYP, TCPTP
Abstract
Protein tyrosine phosphatases (PTPs) play a central role in modulating the transduction of cellular signals, including the cells of the immune system. Several PTPs, PTPN22, PTPN2, and UBASH3A, have been associated with risk of type 1 diabetes (T1D) by genome wide association studies. Based on the current understanding of PTPs, it is clear that these variants impact antigen receptor signaling and cytokine signaling. This impact likely contributes to the development and progression of autoimmunity through multiple mechanisms, including failures of central and peripheral tolerance and the promotion of proinflammatory T cell responses. In this review, we discuss the genetic and functional implications of two of these PTPs, PTPN22 and PTPN2, in the development of T1D. We describe the known roles of these proteins in immune function, and how the expression and function of these proteins is altered by the genetic variants associated with T1D. Yet, there are still controversies in the field that require further study and the development of new approaches to extend our understanding of these PTP variants, with the goal of using the information gained to improve our ability to predict and cure T1D.
Fulltext:
HTML
, PDF
(763KB)
This article has been cited by other articles:
|
Detection of Janus-activated kinase-1 and its interacting proteins by the method of luminescent oxygen channeling
Guo XX, Wu HT, Zhuang SH, Chen ZH, Liang RL, Chen Y, Wu YS, Liu TC
RSC Adv 2017. 7:9639-9644
|
|
|
Concise Review: Cell-Based Therapies and Other Non-Traditional Approaches for Type 1 Diabetes
Creusot RJ, Battaglia M, Roncarolo MG, Fathman CG
Stem Cells 2016. 34(4):809-819
|
|
|
Disease-Specific and Common HLA and Non-HLA Genetic Markers in Susceptibility to Rheumatoid Arthritis, Type 1 Diabetes Mellitus and Multiple Sclerosis
Sjakste T, Kalnina J, Paramonova N, Nikitina-Zake L, Sjakste N
J Mol Genet Med 2016. 10:1
|
|
|
Dissecting diabetes/metabolic disease mechanisms using pluripotent stem cells and genome editing tools
Teo AK, Gupta MK, Doria A, Kulkarni RN
Mol Metab 2015. 4(9):593-604
|
|
|
Genetic Variations of PTPN2 and PTPN22: Role in the Pathogenesis of Type 1 Diabetes and Crohn's Disease
Sharp RC, Abdulrahim M, Naser ES, Naser SA
Front Cell Infect Microbiol 2015. 5:95
|
|
|
Association Between PTPN22 Polymorphisms and IgE Responses to Staphylococcal Superantigens in Chronic Urticaria
Palikhe S, Kim SH, Pham LD, Ye YM, Park HS
Allergy Asthma Immunol Res 2014. 6:e294
|
|
|