The Bcr-Abl tyrosine kinase activates mitogenic signaling pathways and stimulates G1-to-S phase transition in hematopoietic cells.

Journal Article

Bcr-Abl is a constitutively active tyrosine kinase that is expressed in Philadelphia chromosome (Ph1)-positive human leukemias. Bcr-Abl has been shown to inhibit apoptosis and cause anchorage independent growth. However, its ability to activate mitogenic signaling pathways is controversial. Here we show that Bcr-Abl signaling prevents down-regulation of cyclin-dependent kinase activity and cell cycle arrest after growth factor deprivation of hematopoietic progenitor cells. Using an inducible system to regulate Bcr-Abl expression, we also demonstrate that Bcr-Abl expression is sufficient to induce G1-to-S phase transition, DNA synthesis, and activation of cyclin-dependent kinases in cells that were arrested in G0 by growth factor deprivation. Furthermore, Bcr-Abl activates Ras, Erk, and Jnk pathways as a primary consequence of expression. These data show that Bcr-Abl is one of a select group of oncogenes that is capable of both inhibiting apoptosis and deregulating cell proliferation. The combination of these activities is likely to be important for the progression of CML.

Full Text

Duke Authors

Cited Authors

  • Cortez, D; Reuther, G; Pendergast, AM

Published Date

  • November 6, 1997

Published In

Volume / Issue

  • 15 / 19

Start / End Page

  • 2333 - 2342

PubMed ID

  • 9393877

International Standard Serial Number (ISSN)

  • 0950-9232

Language

  • eng

Conference Location

  • England