The roles of protein tyrosine phosphatases in bone-resorbing osteoclasts

Moran Shalev; Ari Elson

doi:10.1016/j.bbamcr.2018.07.005

The roles of protein tyrosine phosphatases in bone-resorbing osteoclasts

Biochim Biophys Acta Mol Cell Res. 2019 Jan;1866(1):114-123. doi: 10.1016/j.bbamcr.2018.07.005. Epub 2018 Jul 17.

Authors

Moran Shalev¹, Ari Elson²

Affiliations

¹ Department of Molecular Genetics, The Weizmann Institute of Science, Rehovot 76100, Israel.
² Department of Molecular Genetics, The Weizmann Institute of Science, Rehovot 76100, Israel. Electronic address: ari.elson@weizmann.ac.il.

PMID: 30026076
DOI: 10.1016/j.bbamcr.2018.07.005

Abstract

Maintaining the proper balance between osteoblast-mediated production of bone and its degradation by osteoclasts is essential for health. Osteoclasts are giant phagocytic cells that are formed by fusion of monocyte-macrophage precursor cells; mature osteoclasts adhere to bone tightly and secrete protons and proteases that degrade its matrix. Phosphorylation of tyrosine residues in proteins, which is regulated by the biochemically-antagonistic activities of protein tyrosine kinases and protein tyrosine phosphatases (PTPs), is central in regulating the production of osteoclasts and their bone-resorbing activity. Here we review the roles of individual PTPs of the classical and dual-specificity sub-families that are known to support these processes (SHP2, cyt-PTPe, PTPRO, PTP-PEST, CD45) or to inhibit them (SHP1, PTEN, MKP1). Characterizing the functions of PTPs in osteoclasts is essential for complete molecular level understanding of bone resorption and for designing novel therapeutic approaches for treating bone disease.

Keywords: Bone resorption; Osteoclast; Osteoporosis; PTP; Tyrosine phosphatase.

Publication types

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

MeSH terms

Animals
Bone Resorption / enzymology
Bone Resorption / metabolism*
Cell Differentiation / physiology
Cell Growth Processes / physiology
Cell Proliferation
Humans
Osteoclasts / cytology
Osteoclasts / metabolism*
PTEN Phosphohydrolase / metabolism
Phosphorylation
Protein Tyrosine Phosphatase, Non-Receptor Type 11 / metabolism
Protein Tyrosine Phosphatase, Non-Receptor Type 6 / metabolism
Protein Tyrosine Phosphatases / metabolism*
Protein Tyrosine Phosphatases / physiology
Protein-Tyrosine Kinases / metabolism
Receptor-Like Protein Tyrosine Phosphatases / metabolism
Receptor-Like Protein Tyrosine Phosphatases, Class 3 / metabolism
Signal Transduction

Substances

Protein-Tyrosine Kinases
Protein Tyrosine Phosphatase, Non-Receptor Type 11
Protein Tyrosine Phosphatase, Non-Receptor Type 6
Protein Tyrosine Phosphatases
Receptor-Like Protein Tyrosine Phosphatases
Receptor-Like Protein Tyrosine Phosphatases, Class 3
PTEN Phosphohydrolase