Endogenous cAbl regulates receptor endocytosis

Michele Jacob, Leslie A. Todd, R. Sonali Majumdar, Yingzhu Li, Ken ichi Yamamoto, Ellen Puré

Research output: Contribution to journalArticle

12 Citations (Scopus)

Abstract

There are two key processes underlying ligand-induced receptor endocytosis: receptor ubiquitylation and remodeling of the actin cytoskeleton. Tyrosine kinases play critical roles in both receptor endocytosis and actin reorganization. Interestingly, members of the Abl family are the only known tyrosine kinases that possess an actin-binding domain and thus have the potential to directly regulate the actin cytoskeleton. However, the role of non-transforming cAbl in receptor endocytosis remains undefined. We report that cAbl promotes ligand-induced antigen receptor endocytosis in B lymphocytes. We show that pharmacologic inhibition or genetic deletion of cAbl causes a defect in tyrosine phosphorylation of the cytoskeletal adapter CrkII. cAbl inhibition or ablation also impairs Rac activation downstream of CrkII, as well as antigen receptor capping and endocytosis. Although phosphorylation of CrkII has been suggested to maintain it in a closed inactive conformation, we demonstrate that it is in fact essential for the activation of Rac. On the other hand, association of CrkII with cCbl, a key mediator of receptor ubiquitylation, does not require CrkII phosphorylation and is cAbl-independent. Phosphorylation of cCbl itself is also cAbl-independent. Our results thus indicate that CrkII links receptor engagement to cytoskeletal remodeling by coupling cCbl- and cAbl-mediated signaling pathways that cooperatively regulate ligand-induced receptor endocytosis.

Original languageEnglish
Pages (from-to)1308-1316
Number of pages9
JournalCellular Signalling
Volume21
Issue number8
DOIs
Publication statusPublished - Aug 1 2009
Externally publishedYes

Keywords

  • Actin
  • BCR
  • Crk
  • Cytoskeleton
  • GTPase

ASJC Scopus subject areas

  • Cell Biology

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  • Cite this

    Jacob, M., Todd, L. A., Majumdar, R. S., Li, Y., Yamamoto, K. I., & Puré, E. (2009). Endogenous cAbl regulates receptor endocytosis. Cellular Signalling, 21(8), 1308-1316. https://doi.org/10.1016/j.cellsig.2009.03.016