title: Protein Tyrosine Phosphatases in Systemic Sclerosis: Potential Pathogenic Players and Therapeutic Targets.
abstract: OBJECTIVE
  The pathogenesis of systemic sclerosis depends on a complex interplay between autoimmunity, vasculopathy, and fibrosis. Reversible phosphorylation on tyrosine residues, in response to growth factors and other stimuli, critically regulates each one of these three key pathogenic processes. Protein tyrosine kinases, the enzymes that catalyze addition of phosphate to tyrosine residues, are known players in systemic sclerosis, and tyrosine kinase inhibitors are undergoing clinical trials for treatment of this disease. Until recently, the role of tyrosine phosphatases-the enzymes that counteract the action of tyrosine kinases by removing phosphate from tyrosine residues-in systemic sclerosis has remained largely unknown. Here, we review the function of tyrosine phosphatases in pathways relevant to the pathogenesis of systemic sclerosis and their potential promise as therapeutic targets to halt progression of this debilitating rheumatic disease.
  
  
  RESULTS
  Protein tyrosine phosphatases are emerging as important regulators of a multitude of signaling pathways and undergoing validation as molecular targets for cancer and other common diseases. Recent advances in drug discovery are paving the ways to develop new classes of tyrosine phosphatase modulators to treat human diseases. Although so far only few reports have focused on tyrosine phosphatases in systemic sclerosis, these enzymes play a role in multiple pathways relevant to disease pathogenesis. Further studies in this field are warranted to explore the potential of tyrosine phosphatases as drug targets for systemic sclerosis.
authors.affiliation: Division of Rheumatology, Allergy and Immunology, Department of Medicine, University of California, San Diego, 9500 Gilman Drive MC #0656, La Jolla, CA, 92093, USA.
authors.forename: Cristiano
authors.initials: C
authors.lastname: Sacchetti
authors.affiliation: Division of Rheumatology, Allergy and Immunology, Department of Medicine, University of California, San Diego, 9500 Gilman Drive MC #0656, La Jolla, CA, 92093, USA. nbottini@ucsd.edu.
authors.forename: Nunzio
authors.initials: N
authors.lastname: Bottini
mesh_terms: D004730:Endothelium, Vascular / Q000503:physiopathology; D004791:Enzyme Inhibitors / Q000627:therapeutic use; D005355:Fibrosis; D006133:Growth Substances / Q000502:physiology; D006801:Humans; D058990:Molecular Targeted Therapy / Q000379:methods*; D017027:Protein Tyrosine Phosphatases / Q000037:antagonists & inhibitors / Q000502:physiology*; D018123:Receptors, Interleukin / Q000276:immunology; D012595:Scleroderma, Systemic / Q000188:drug therapy / Q000201:enzymology* / Q000276:immunology; D015398:Signal Transduction / Q000276:immunology; D057170:Translational Research, Biomedical / Q000379:methods
chemical_list: D004791:Enzyme Inhibitors; D006133:Growth Substances; D018123:Receptors, Interleukin; D017027:Protein Tyrosine Phosphatases
keywords: Molecular target; Protein tyrosine phosphatase; Protein tyrosine phosphorylation; Signal transduction; Systemic sclerosis