Modeling (not so) rare developmental disorders associated with mutations in the protein-tyrosine phosphatase SHP2

Maja Solman; Daniëlle T J Woutersen; Jeroen den Hertog

doi:10.3389/fcell.2022.1046415

Modeling (not so) rare developmental disorders associated with mutations in the protein-tyrosine phosphatase SHP2

Front Cell Dev Biol. 2022 Nov 4:10:1046415. doi: 10.3389/fcell.2022.1046415. eCollection 2022.

Authors

Maja Solman¹, Daniëlle T J Woutersen¹, Jeroen den Hertog^{1

2}

Affiliations

¹ Hubrecht Institute-KNAW, University Medical Center Utrecht, Utrecht, Netherlands.
² Institute Biology Leiden, Leiden University, Leiden, Netherlands.

Abstract

Src homology region 2 (SH2)-containing protein tyrosine phosphatase 2 (SHP2) is a highly conserved protein tyrosine phosphatase (PTP), which is encoded by PTPN11 and is indispensable during embryonic development. Mutations in PTPN11 in human patients cause aberrant signaling of SHP2, resulting in multiple rare hereditary diseases, including Noonan Syndrome (NS), Noonan Syndrome with Multiple Lentigines (NSML), Juvenile Myelomonocytic Leukemia (JMML) and Metachondromatosis (MC). Somatic mutations in PTPN11 have been found to cause cancer. Here, we focus on the role of SHP2 variants in rare diseases and advances in the understanding of its pathogenesis using model systems.

Keywords: Noonan syndrome; Noonan syndrome with multiple lentigenes; SHP2; fruitfly; metachondromatosis; modeling; mouse; zebrafish.

Publication types

Review