SHP2: The protein tyrosine phosphatase involved in chronic pulmonary inflammation and fibrosis

IUBMB Life. 2022 Feb;74(2):131-142. doi: 10.1002/iub.2559. Epub 2021 Sep 30.

Abstract

Chronic respiratory diseases (CRDs), including pulmonary fibrosis, chronic obstructive pulmonary disease (COPD), lung cancer, and asthma, are significant global health problems due to their prevalence and rising incidence. The roles of protein tyrosine kinases (PTKs) and protein tyrosine phosphatases (PTPs) in controlling tyrosine phosphorylation of targeting proteins modulate multiple physiological cellular responses and contribute to the pathogenesis of CRDs. Src homology-2 domain-containing PTP2 (SHP2) plays a pivotal role in modulating downstream growth factor receptor signaling and cytoplasmic PTKs, including MAPK/ERK, PI3K/AKT, and JAK/STAT pathways, to regulate cell survival and proliferation. In addition, SHP2 mutation and activation are commonly implicated in tumorigenesis. However, little is known about SHP2 in chronic pulmonary inflammation and fibrosis. This review discusses the potential involvement of SHP2 deregulation in chronic pulmonary inflammation and fibrosis, as well as the therapeutic effects of targeting SHP2 in CRDs.

Keywords: CRDs; SHP2; fibrosis; inflammation.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Fibrosis
  • Humans
  • Pneumonia* / enzymology
  • Protein Tyrosine Phosphatase, Non-Receptor Type 11* / genetics
  • Protein Tyrosine Phosphatase, Non-Receptor Type 11* / metabolism
  • Respiratory Tract Diseases* / epidemiology
  • Signal Transduction

Substances

  • PTPN11 protein, human
  • Protein Tyrosine Phosphatase, Non-Receptor Type 11