First published online August 16, 2005
Journal of Cell Science 118, 1604e (2005)
© The Company of Biologists Limited
Abl to take the Myc in mitogenesis
Many growth factors stimulate DNA synthesis through Ras/MAP kinase signalling. Src family kinases are also important in growth-factor-induced mitogenic responses. For example, the cytoplasmic tyrosine kinase Abl, a Src substrate, is required for platelet-derived growth factor (PDGF) receptor signalling. Downstream targets of Abl have remained ill defined, however. Serge Roche and co-workers now provide convincing evidence that the small GTPase Rac is an important effector of Abl (see p. 3717) and that Rac acts through NADPH oxidase (Nox) and Jun N-terminal kinase (JNK) signalling to stimulate mitogenesis. The authors show that PDGF-induced Rac activation is impaired in cells with inactive Abl but that constitutive expression of active Rac overcomes the mitogenic defects in these cells, provided they contain functioning JNK and Nox pathways. Furthermore, they find that JNK and Nox co-activation rescues mitogenesis in cells with inactive Abl. The authors also show that Myc is an important target of this signalling cascade and conclude that cytoplasmic Abl acts through a Rac/JNK and a Rac/Nox pathway to induce Myc expression and DNA synthesis in response to PDGF.
Related articles in JCS:
- Abl tyrosine kinase regulates a Rac/JNK and a Rac/Nox pathway for DNA synthesis and Myc expression induced by growth factors
- Anthony Boureux, Olivia Furstoss, Valérie Simon, and Serge Roche
JCS 2005 118: 3717-3726.
[Abstract]
[Full Text]
