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 Citations (Scopus)

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
Pages376-384
Number of pages9
Volume1192
DOIs
StatePublished - Mar 1 2010

Publication series

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

Fingerprint

Phosphatidylinositol 3-Kinase
Macrophage Colony-Stimulating Factor
Osteoclasts
Pseudopodia
Actins
Macrophage Colony-Stimulating Factor Receptors
Phenylalanine
Tyrosine
Bone
Bone Marrow
Ligands

Keywords

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

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

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 (Vol. 1192, pp. 376-384). (Annals of the New York Academy of Sciences; Vol. 1192). https://doi.org/10.1111/j.1749-6632.2009.05346.x

Cbl-phosphatidylinositol 3 kinase interaction differentially regulates macrophage colony-stimulating factor-mediated osteoclast survival and cytoskeletal reorganization. / Adapala, Naga Suresh; Barbe, Mary F.; Langdon, Wallace Y.; Tsygankov, Alexander Y.; Sanjay, Archana.

Skeletal Biology and Medicine. Vol. 1192 2010. p. 376-384 (Annals of the New York Academy of Sciences; Vol. 1192).

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

Adapala, NS, Barbe, MF, Langdon, WY, Tsygankov, AY & 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. vol. 1192, Annals of the New York Academy of Sciences, vol. 1192, pp. 376-384. https://doi.org/10.1111/j.1749-6632.2009.05346.x
Adapala NS, Barbe MF, Langdon WY, Tsygankov AY, Sanjay A. Cbl-phosphatidylinositol 3 kinase interaction differentially regulates macrophage colony-stimulating factor-mediated osteoclast survival and cytoskeletal reorganization. In Skeletal Biology and Medicine. Vol. 1192. 2010. p. 376-384. (Annals of the New York Academy of Sciences). https://doi.org/10.1111/j.1749-6632.2009.05346.x
Adapala, Naga Suresh ; Barbe, Mary F. ; Langdon, Wallace Y. ; Tsygankov, Alexander Y. ; Sanjay, Archana. / Cbl-phosphatidylinositol 3 kinase interaction differentially regulates macrophage colony-stimulating factor-mediated osteoclast survival and cytoskeletal reorganization. Skeletal Biology and Medicine. Vol. 1192 2010. pp. 376-384 (Annals of the New York Academy of Sciences).
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