Regulation of the formation of osteoclastic actin rings by proline-rich tyrosine kinase 2 interacting with gelsolin

Qiang Wang, Yi Xie, Quansheng Du, Xiao Jun Wu, Xu Feng, Lin Mei, Jay M. McDonald, Wencheng Xiong

Research output: Contribution to journalArticle

86 Citations (Scopus)

Abstract

Osteoclast activation is important for bone remodeling and is altered in multiple bone disorders. This process requires cell adhesion and extensive actin cytoskeletal reorganization. Proline-rich tyrosine kinase 2 (PYK2), a major cell adhesion-activated tyrosine kinase in osteoclasts, plays an important role in regulating this event. The mechanisms by which PYK2 regulates actin cytoskeletal organization and osteoclastic activation remain largely unknown. In this paper, we provide evidence that PYK2 directly interacts with gelsolin, an actin binding, severing, and capping protein essential for osteoclastic actin cytoskeletal organization. The interaction is mediated via the focal adhesion-targeting domain of PYK2 and an LD motif in gelsolin's COOH terminus. PYK2 phosphorylates gelsolin at tyrosine residues and regulates gelsolin bioactivity, including decreasing gelsolin binding to actin monomer and increasing gelsolin binding to phosphatidylinositol lipids. In addition, PYK2 increases actin polymerization at the fibroblastic cell periphery. Finally, PYK2 interacts with gelsolin in osteoclasts, where PYK2 activation is required for the formation of actin rings. Together, our results suggest that PYK2 is a regulator of gelsolin, revealing a novel PYK2-gelsolin pathway in regulating actin cytoskeletal organization in multiple cells, including osteoclasts.

Original languageEnglish (US)
Pages (from-to)565-575
Number of pages11
JournalJournal of Cell Biology
Volume160
Issue number4
DOIs
StatePublished - Feb 17 2003

Fingerprint

Focal Adhesion Kinase 2
Gelsolin
Actins
Osteoclasts
Cell Adhesion
Actin Capping Proteins
Microfilament Proteins
Focal Adhesions
Bone Remodeling
Phosphatidylinositols
Polymerization
Protein-Tyrosine Kinases
Tyrosine

Keywords

  • Actin cytoskeleton
  • FAK
  • Focal adhesions
  • PYK2
  • Podosomes

ASJC Scopus subject areas

  • Cell Biology

Cite this

Regulation of the formation of osteoclastic actin rings by proline-rich tyrosine kinase 2 interacting with gelsolin. / Wang, Qiang; Xie, Yi; Du, Quansheng; Wu, Xiao Jun; Feng, Xu; Mei, Lin; McDonald, Jay M.; Xiong, Wencheng.

In: Journal of Cell Biology, Vol. 160, No. 4, 17.02.2003, p. 565-575.

Research output: Contribution to journalArticle

Wang, Qiang ; Xie, Yi ; Du, Quansheng ; Wu, Xiao Jun ; Feng, Xu ; Mei, Lin ; McDonald, Jay M. ; Xiong, Wencheng. / Regulation of the formation of osteoclastic actin rings by proline-rich tyrosine kinase 2 interacting with gelsolin. In: Journal of Cell Biology. 2003 ; Vol. 160, No. 4. pp. 565-575.
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