Cbl-phosphatidylinositol 3 kinase interaction differentially regulates macrophage colony-stimulating factor-mediated osteoclast survival and cytoskeletal reorganization

Naga Suresh Adapala, Mary F. Barbe, Wallace Y. Langdon, Alexander Y. Tsygankov, Archana Sanjay

Research output: Chapter in Book/Report/Conference proceedingConference contribution

13 Scopus citations

Abstract

The Cbl protein is a key player in macrophage colony-stimulating factor (M-CSF)-induced signaling. To examine the role of Cbl in M-CSF-mediated cellular events, we used CblYF/YF knockin mice in which the regulatory tyrosine 737, which when phosphorylated binds to the p85 subunit of phosphatidylinositol 3 kinase (PI3K), is substituted to phenylalanine. In ex vivo cultures, M-CSF and receptor activator of nuclear factor-κB ligand-mediated differentiation of bone marrow precursors from Cbl YF/YF mice generated increased number of osteoclasts; however, osteoclast numbers in CblYF/YF cultures were unchanged with increasing doses of M-CSF. We found that CblYF/YF osteoclasts have enhanced intrinsic ability to survive, and this response was further augmented upon exposure to M-CSF. Treatment of osteoclasts with M-CSF-induced actin reorganization and lamellipodia formation in wild-type osteoclasts; however, in CblYF/YF osteoclasts lamellipodia formation was compromised. Collectively, these results indicate that abrogation of the Cbl-PI3K interaction, although not affecting M-CSF-induced proliferation and differentiation of precursors, is required for regulation of survival and actin cytoskeletal reorganization of mature osteoclasts.

Original languageEnglish (US)
Title of host publicationSkeletal Biology and Medicine
PublisherBlackwell Publishing Inc.
Pages376-384
Number of pages9
ISBN (Print)9781573317856
DOIs
StatePublished - Mar 2010

Publication series

NameAnnals of the New York Academy of Sciences
Volume1192
ISSN (Print)0077-8923
ISSN (Electronic)1749-6632

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Keywords

  • Cbl
  • M-CSF
  • Osteoclast
  • PI3K
  • Survival

ASJC Scopus subject areas

  • Neuroscience(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • History and Philosophy of Science

Cite this

Adapala, N. S., Barbe, M. F., Langdon, W. Y., Tsygankov, A. Y., & Sanjay, A. (2010). Cbl-phosphatidylinositol 3 kinase interaction differentially regulates macrophage colony-stimulating factor-mediated osteoclast survival and cytoskeletal reorganization. In Skeletal Biology and Medicine (pp. 376-384). (Annals of the New York Academy of Sciences; Vol. 1192). Blackwell Publishing Inc.. https://doi.org/10.1111/j.1749-6632.2009.05346.x