Journal article
Activation of Src Family Members Is Not Required for the Platelet-Derived Growth Factor β Receptor To Initiate Mitogenesis
Molecular and cellular biology, Vol.18(4), pp.2014-2022
04/1998
DOI: 10.1128/MCB.18.4.2014
PMCID: PMC121431
PMID: 9528773
Abstract
The basal activity of Src family kinases is readily detectable throughout the cell cycle and increases by two- to fivefold upon acute stimulation of cells with growth factors such as platelet-derived growth factor. Previous reports have demonstrated a requirement for Src activity for the G1/S and G2/M transitions. With a chimeric α-β PDGF receptor (PDGFR) expressed in fibroblasts, we have investigated the importance of the PDGF-mediated increase in Src activity at the G0/G1 transition for subsequent cell cycle events. A mutant PDGFR chimera that was not able to detectably associate with or activate Src was compromised in its ability to mediate tyrosine phosphorylation of receptor-associated signaling molecules and initiated a submaximal activation of Erk. In contrast to these early cell cycle events, later responses such as entry of cells into S phase and cell proliferation proceeded normally when Src activity did not increase following acute stimulation with PDGF. We conclude that the initial burst of Src activity is required for efficient tyrosine phosphorylation of receptor-associated proteins such as PLCγ, RasGAP, Shc, and SHP-2 and for maximal activation of Erk. Surprisingly, these events are not required for PDGF-dependent cell proliferation. Finally, later cell cycle events do not require that Src be activated at the G0/G1 transition and leave open the possibility that events such as the G1/S transition require the basal Src activity and/or activation of Src at later times in G1.
Details
- Title: Subtitle
- Activation of Src Family Members Is Not Required for the Platelet-Derived Growth Factor β Receptor To Initiate Mitogenesis
- Creators
- Kris A DeMali - Schepens Eye Research Institute, Harvard Medical School, Boston, Massachusetts 02114, and University of Colorado Health Sciences Center, Department of Pharmacology, Denver, Colorado 80206Andrius Kazlauskas - Schepens Eye Research Institute, Harvard Medical School, Boston, Massachusetts 02114, and University of Colorado Health Sciences Center, Department of Pharmacology, Denver, Colorado 80206
- Resource Type
- Journal article
- Publication Details
- Molecular and cellular biology, Vol.18(4), pp.2014-2022
- DOI
- 10.1128/MCB.18.4.2014
- PMID
- 9528773
- PMCID
- PMC121431
- NLM abbreviation
- Mol Cell Biol
- ISSN
- 0270-7306
- eISSN
- 1098-5549
- Publisher
- American Society for Microbiology
- Language
- English
- Date published
- 04/1998
- Academic Unit
- Dermatology; Fraternal Order of Eagles Diabetes Research Center; Biochemistry and Molecular Biology
- Record Identifier
- 9984025248502771
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