Journal article
c-Abl is activated by growth factors and Src family kinases and has a role in the cellular response to PDGF
Genes & development, Vol.13(18), pp.2400-2411
09/15/1999
DOI: 10.1101/gad.13.18.2400
PMCID: PMC317022
PMID: 10500097
Abstract
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.
Details
- Title: Subtitle
- c-Abl is activated by growth factors and Src family kinases and has a role in the cellular response to PDGF
- Creators
- Rina Plattner - Department of Pharmacology and Cancer Biology, Duke University Medical Center, Durham, North Carolina 27710 USALisa Kadlec - Department of Pharmacology and Cancer Biology, Duke University Medical Center, Durham, North Carolina 27710 USAKris A DeMali - Department of Pharmacology and Cancer Biology, Duke University Medical Center, Durham, North Carolina 27710 USAAndrius Kazlauskas - Department of Pharmacology and Cancer Biology, Duke University Medical Center, Durham, North Carolina 27710 USAAnn Marie Pendergast - Department of Pharmacology and Cancer Biology, Duke University Medical Center, Durham, North Carolina 27710 USA
- Resource Type
- Journal article
- Publication Details
- Genes & development, Vol.13(18), pp.2400-2411
- Publisher
- Cold Spring Harbor Laboratory Press
- DOI
- 10.1101/gad.13.18.2400
- PMID
- 10500097
- PMCID
- PMC317022
- ISSN
- 0890-9369
- eISSN
- 1549-5477
- Language
- English
- Date published
- 09/15/1999
- Academic Unit
- Dermatology; Fraternal Order of Eagles Diabetes Research Center; Biochemistry and Molecular Biology
- Record Identifier
- 9984024514802771
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