PDGF receptor-to-nucleus signaling of p91 (STAT1 alpha) transcription factor in rat smooth muscle cells.
Vascular smooth muscle cells (VSMC) are the predominant cell type in the media of a normal artery. Injury to the vessel wall leads to platelet deposition and the release of numerous factors, including PDGF, which exerts its biological effects by binding to specific surface receptors on the smooth muscle cell membrane. We demonstrate that PDGF-stimulated smooth muscle cells activate the STAT (signal transducers and activators of transcription) family of proteins in addition to other signaling pathways (e.g., RAS-RAF-MAP Kinase). We show that the transcription factor p91 (STAT1 alpha) is rapidly activated by PDGF in VSMC and specifically binds to the regulatory elements SIE or GAS. We hypothesize that signal transduction by p91 plays an important role in VSMC, especially after injury with the release of growth factors such as PDGF.
Yamamoto
H
H
Laboratory of Cardiovascular Sciences, National Institute on Aging, National Institute of Health, Baltimore, Maryland 21224, USA.
Crow
M
M
Cheng
L
L
Lakatta
E
E
Kinsella
J
J
D000818:Animals; D001483:Base Sequence; D000077214:Becaplermin; D002467:Cell Nucleus / Q000737:chemistry / Q000378:metabolism*; D002478:Cells, Cultured; D004247:DNA / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000032:analysis / Q000378:metabolism* / Q000502:physiology; D017930:Genes, Reporter; D050832:Interferon-Stimulated Gene Factor 3; D008156:Luciferases / Q000096:biosynthesis / Q000235:genetics; D008969:Molecular Sequence Data; D009131:Muscle, Smooth, Vascular / Q000166:cytology / Q000502:physiology*; D010766:Phosphorylation; D010982:Platelet-Derived Growth Factor / Q000378:metabolism; D011401:Promoter Regions, Genetic / Q000502:physiology; D020574:Proto-Oncogene Proteins c-sis; D051381:Rats; D017479:Receptors, Platelet-Derived Growth Factor / Q000378:metabolism* / Q000502:physiology; D011993:Recombinant Fusion Proteins / Q000096:biosynthesis; D015398:Signal Transduction / Q000502:physiology*; D014157:Transcription Factors / Q000032:analysis / Q000378:metabolism* / Q000502:physiology; D015533:Transcriptional Activation / Q000502:physiology; D014443:Tyrosine / Q000378:metabolism
D004268:DNA-Binding Proteins; D050832:Interferon-Stimulated Gene Factor 3; D010982:Platelet-Derived Growth Factor; D020574:Proto-Oncogene Proteins c-sis; D011993:Recombinant Fusion Proteins; D014157:Transcription Factors; C079868:gamma interferon activation factor; D000077214:Becaplermin; D014443:Tyrosine; D004247:DNA; D008156:Luciferases; D017479:Receptors, Platelet-Derived Growth Factor