TULA-2, a novel histidine phosphatase, regulates bone remodeling by modulating osteoclast function

Steven H. Back, Naga Suresh Adapala, Mary F. Barbe, Nick C. Carpino, Alexander Y. Tsygankov, Archana Sanjay

Research output: Contribution to journalArticle

15 Citations (Scopus)

Abstract

Bone is a dynamic tissue that depends on the intricate relationship between protein tyrosine kinases (PTK) and protein tyrosine phosphatases (PTP) for maintaining homeostasis. PTKs and PTPs act like molecular on and off switches and help modulate differentiation and the attachment of osteoclasts to bone matrix regulating bone resorption. The protein T cell ubiquitin ligand-2 (TULA-2), which is abundantly expressed in osteoclasts, is a novel histidine phosphatase. Our results show that of the two family members, only TULA-2 is expressed in osteoclasts and that its expression is sustained throughout the course of osteoclast differentiation, suggesting that TULA-2 may play a role during early as well late stages of osteoclast differentiation. Skeletal analysis of mice that do not express TULA or TULA-2 proteins (DKO mice) revealed that there was a decrease in bone volume due to increased osteoclast numbers and function. Furthermore, in vitro experiments indicated that bone marrow precursor cells from DKO mice have an increased potential to form osteoclasts. At the molecular level, the absence of TULA-2 in osteoclasts results in increased Syk phosphorylation at the Y352 and Y525/526 residues and activation of phospholipase C gamma 2 (PLCγ2) upon engagement of immune-receptor- tyrosine-based-activation-motif (ITAM) - mediated signaling. Furthermore, expression of a phosphatase-dead TULA-2 leads to increased osteoclast function. Taken together, these results suggest that TULA-2 negatively regulates osteoclast differentiation and function.

Original languageEnglish (US)
Pages (from-to)1269-1284
Number of pages16
JournalCellular and Molecular Life Sciences
Volume70
Issue number7
DOIs
StatePublished - Apr 1 2013

Fingerprint

Bone Remodeling
Osteoclasts
Ubiquitin
Phosphoric Monoester Hydrolases
Histidine
Ligands
T-Lymphocytes
Immunoreceptor Tyrosine-Based Activation Motif
Phospholipase C gamma
Bone and Bones
Bone Matrix
Protein Tyrosine Phosphatases
Bone Resorption
Bone Marrow Cells
Protein-Tyrosine Kinases
Proteins
Homeostasis
Phosphorylation

Keywords

  • Fc receptor
  • ITAM
  • PLCγ
  • Syk
  • Tyrosine kinase

ASJC Scopus subject areas

  • Cell Biology
  • Molecular Biology
  • Molecular Medicine
  • Pharmacology
  • Cellular and Molecular Neuroscience

Cite this

TULA-2, a novel histidine phosphatase, regulates bone remodeling by modulating osteoclast function. / Back, Steven H.; Adapala, Naga Suresh; Barbe, Mary F.; Carpino, Nick C.; Tsygankov, Alexander Y.; Sanjay, Archana.

In: Cellular and Molecular Life Sciences, Vol. 70, No. 7, 01.04.2013, p. 1269-1284.

Research output: Contribution to journalArticle

Back, Steven H. ; Adapala, Naga Suresh ; Barbe, Mary F. ; Carpino, Nick C. ; Tsygankov, Alexander Y. ; Sanjay, Archana. / TULA-2, a novel histidine phosphatase, regulates bone remodeling by modulating osteoclast function. In: Cellular and Molecular Life Sciences. 2013 ; Vol. 70, No. 7. pp. 1269-1284.
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