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Assessment of Mitochondrial Functions and Cell Viability in Renal Cells Overexpressing Protein Kinase C Isozymes
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Cdo binds Abl to promote p38alpha/beta mitogen-activated protein kinase activity and myogenic differentiation

Gyu-Un Bae1, Bok-Geon Kim, Hye-Jin Lee

  • 1Department of Developmental and Regenerative Biology, Mount Sinai School of Medicine, New York, NY 10029, USA. Robert.Krauss@mssm.edu

Molecular and Cellular Biology
|May 28, 2009
PubMed

Insights

The tyrosine kinase Abl and cell surface receptor Cdo promote skeletal muscle cell differentiation by activating the p38 MAPK pathway. This interaction involves a multiprotein complex regulating cell differentiation.

Area of Science:

  • Cell Biology
  • Molecular Biology
  • Biochemistry

Background:

  • The p38 MAPK pathway is crucial for skeletal myoblast differentiation.
  • The precise mechanisms activating this pathway during differentiation are not fully understood.
  • The tyrosine kinase Abl is known to promote myogenic differentiation, but its interacting partners remain unidentified.

Purpose of the Study:

  • To investigate the interaction between Abl and cell surface proteins during myoblast differentiation.
  • To elucidate the role of Abl in the activation of the p38 MAPK pathway.
  • To identify the signaling proteins involved in Abl-mediated myogenic differentiation.

Main Methods:

  • Co-immunoprecipitation assays to detect protein interactions.
  • Analysis of Abl and Cdo binding domains (SH3 domain and proline-rich motif).
  • Knockdown studies using siRNA to deplete Abl and Cdo.
  • Rescue experiments using activated MAPK kinase 6.

Main Results:

  • Abl associates with Cdo and JLP during skeletal myoblast differentiation.
  • Abl binds Cdo via its SH3 domain, and both proteins are essential for their promyogenic effects.
  • Cdo enhances Abl kinase activity, and Abl is necessary for full p38 MAPK activation.
  • Depletion of Abl or Cdo impairs differentiation, which can be rescued by activating downstream signaling.

Conclusions:

  • Abl's promyogenic activity is mediated by a cell surface complex involving Cdo and JLP.
  • This complex regulates the differentiation-dependent activation of the p38 MAPK pathway.
  • Abl and Cdo are key regulators of skeletal muscle differentiation through p38 MAPK signaling.

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