Dynamin and PTP-PEST cooperatively regulate Pyk2 dephosphorylation in osteoclasts

Pierre P. Eleniste, Liping Du, Mahesh Shivanna, Angela Bruzzaniti

Research output: Contribution to journalArticle

12 Citations (Scopus)

Abstract

Bone loss is caused by the dysregulated activity of osteoclasts which degrade the extracellular bone matrix. The tyrosine kinase Pyk2 is highly expressed in osteoclasts, and mice lacking Pyk2 exhibit an increase in bone mass, in part due to impairment of osteoclast function. Pyk2 is activated by phosphorylation at Y402 following integrin activation, but the mechanisms leading to Pyk2 dephosphorylation are poorly understood. In the current study, we examined the mechanism of action of the dynamin GTPase on Pyk2 dephosphorylation. Our studies reveal a novel mechanism for the interaction of Pyk2 with dynamin, which involves the binding of Pyk2's FERM domain with dynamin's plextrin homology domain. In addition, we demonstrate that the dephosphorylation of Pyk2 requires dynamin's GTPase activity and is mediated by the tyrosine phosphatase PTP-PEST. The dephosphorylation of Pyk2 by dynamin and PTP-PEST may be critical for terminating outside-in integrin signaling, and for stabilizing cytoskeletal reorganization during osteoclast bone resorption.

Original languageEnglish (US)
Pages (from-to)790-800
Number of pages11
JournalInternational Journal of Biochemistry and Cell Biology
Volume44
Issue number5
DOIs
StatePublished - May 2012

Fingerprint

Non-Receptor Type 12 Protein Tyrosine Phosphatase
Dynamins
Osteoclasts
Bone
GTP Phosphohydrolases
Integrins
Bone and Bones
Phosphorylation
Bone Matrix
Bone Resorption
Phosphoric Monoester Hydrolases
Protein-Tyrosine Kinases
Extracellular Matrix
Tyrosine
Chemical activation

Keywords

  • Osteoclasts
  • Phosphatase
  • Phosphorylation
  • Signaling
  • Tyrosine kinase

ASJC Scopus subject areas

  • Biochemistry
  • Cell Biology

Cite this

Dynamin and PTP-PEST cooperatively regulate Pyk2 dephosphorylation in osteoclasts. / Eleniste, Pierre P.; Du, Liping; Shivanna, Mahesh; Bruzzaniti, Angela.

In: International Journal of Biochemistry and Cell Biology, Vol. 44, No. 5, 05.2012, p. 790-800.

Research output: Contribution to journalArticle

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