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c-Abl is activated by growth factors and Src family kinases and has a role in the cellular response to PDGF.

Publication ,  Journal Article
Plattner, R; Kadlec, L; DeMali, KA; Kazlauskas, A; Pendergast, AM
Published in: Genes Dev
September 15, 1999

The c-Abl tyrosine kinase localizes to the cytoplasm and plasma membrane in addition to the nucleus. However, there is little information regarding a role for c-Abl in the cytoplasm/plasma membrane compartments. Here we report that a membrane pool of c-Abl is activated by the growth factors PDGF and EGF in fibroblasts. The pattern and kinetics of activation are similar to growth factor activation of Src family kinases. To determine whether a link existed between activation of c-Abl and members of the Src family, we examined c-Abl kinase activity in cells that expressed oncogenic Src proteins. We found that c-Abl kinase activity was increased by 10- to 20-fold in these cells, and that Src and Fyn kinases directly phosphorylated c-Abl in vitro. Furthermore, overexpression of wild-type Src potentiated c-Abl activation by growth factors, and a kinase-inactive form of Src reduced this activation, showing that Abl activation by growth factors occurs at least in part via activation of Src kinases. Significantly, we show that c-Abl has a functional role in the morphological response to PDGF. Whereas PDGF treatment of serum-starved wild-type mouse embryo fibroblasts resulted in distinct linear or circular/dorsal membrane ruffling, c-Abl-null cells demonstrated dramatically reduced ruffling in response to PDGF, which was rescued by physiological re-expression of c-Abl. These data identify c-Abl as a downstream target of activated receptor tyrosine kinases and Src family kinases, and show for the first time that c-Abl functions in the cellular response to growth factors.

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Published In

Genes Dev

DOI

ISSN

0890-9369

Publication Date

September 15, 1999

Volume

13

Issue

18

Start / End Page

2400 / 2411

Location

United States

Related Subject Headings

  • src-Family Kinases
  • Tumor Cells, Cultured
  • Time Factors
  • Rats
  • Proto-Oncogene Proteins c-abl
  • Precipitin Tests
  • Platelet-Derived Growth Factor
  • Phosphorylation
  • Mice
  • Humans
 

Citation

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Plattner, R., Kadlec, L., DeMali, K. A., Kazlauskas, A., & Pendergast, A. M. (1999). c-Abl is activated by growth factors and Src family kinases and has a role in the cellular response to PDGF. Genes Dev, 13(18), 2400–2411. https://doi.org/10.1101/gad.13.18.2400
Plattner, R., L. Kadlec, K. A. DeMali, A. Kazlauskas, and A. M. Pendergast. “c-Abl is activated by growth factors and Src family kinases and has a role in the cellular response to PDGF.Genes Dev 13, no. 18 (September 15, 1999): 2400–2411. https://doi.org/10.1101/gad.13.18.2400.
Plattner R, Kadlec L, DeMali KA, Kazlauskas A, Pendergast AM. c-Abl is activated by growth factors and Src family kinases and has a role in the cellular response to PDGF. Genes Dev. 1999 Sep 15;13(18):2400–11.
Plattner, R., et al. “c-Abl is activated by growth factors and Src family kinases and has a role in the cellular response to PDGF.Genes Dev, vol. 13, no. 18, Sept. 1999, pp. 2400–11. Pubmed, doi:10.1101/gad.13.18.2400.
Plattner R, Kadlec L, DeMali KA, Kazlauskas A, Pendergast AM. c-Abl is activated by growth factors and Src family kinases and has a role in the cellular response to PDGF. Genes Dev. 1999 Sep 15;13(18):2400–2411.

Published In

Genes Dev

DOI

ISSN

0890-9369

Publication Date

September 15, 1999

Volume

13

Issue

18

Start / End Page

2400 / 2411

Location

United States

Related Subject Headings

  • src-Family Kinases
  • Tumor Cells, Cultured
  • Time Factors
  • Rats
  • Proto-Oncogene Proteins c-abl
  • Precipitin Tests
  • Platelet-Derived Growth Factor
  • Phosphorylation
  • Mice
  • Humans