Cited by 192Protein Kinase Regulation and GTPase SignalingAngiogenesis and VEGF in CancerTGF-β signaling in diseases

Additive Effects of PDGF Receptor β Signaling Pathways in Vascular Smooth Muscle Cell Development

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Tallquist, Michelle D, French, Wendy J, Soriano, Philippe·2003·PLoS Biology

Abstract

The platelet-derived growth factor beta receptor (PDGFRbeta) is known to activate many molecules involved in signal transduction and has been a paradigm for receptor tyrosine kinase signaling for many years. We have sought to determine the role of individual signaling components downstream of this receptor in vivo by analyzing an allelic series of tyrosine-phenylalanine mutations that prevent binding of specific signal transduction components. Here we show that the incidence of vascular smooth muscle cells/pericytes (v/p), a PDGFRbeta-dependent cell type, can be correlated to the amount of receptor expressed and the number of activated signal transduction pathways. A decrease in either receptor expression levels or disruption of multiple downstream signaling pathways lead to a significant reduction in v/p. Conversely, loss of RasGAP binding leads to an increase in this same cell population, implicating a potential role for this effector in attenuating the PDGFRbeta signal. The combined in vivo and biochemical data suggest that the summation of pathways associated with the PDGFRbeta signal transduction determines the expansion of developing v/p cells.

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Crossref · 10.1371/journal.pbio.0000052

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  • Pericyte-deficient mouse models caused by aberrant PDGF-BB/PDGFRβ signaling exhibit impaired BBB formation and maintenance.

    “Pericytedeficient mouse models caused by aberrant PDGF-BB/ PDGFR𝛃 signaling (365, 419, 436, 570, 575) exhibit impaired BBB formation (28, 59, 130) and maintenance (59, 436).”

    From Blood-Brain Barrier: From Physiology to Disease and Back (2019) · cites this paper as [575]

    The Results (V/P Development; page unavailable) show that PDGFRβ-mutant mice have reduced pericyte numbers, including in the developing nervous system. The Introduction identifies brain pericytes as PDGFRβ-dependent. However, the paper does not report impaired blood–brain barrier formation or maintenance in these mice; its reported vascular defects do not establish that specific outcome. (LLM, conf=0.86)

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Research works printed but not linked: 2

  1. Tallquist MD Soriano P Epiblast-restricted Cre expression in MORE mice: A tool to distinguish embryonic vs. extra-embryonic gene function Genesis 2000 26 113 115 10686601
  2. Tidhar A Reichenstein M Cohen D Faerman A Copeland NG A novel transgenic marker for migrating limb muscle precursors and for vascular smooth muscle cells Dev Dyn 2001 220 60 73 11146508

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Authors
Tallquist, M. D., French, W. J., & Soriano, P.
Affiliations
  • Fred Hutch Cancer Center (US)
  • The University of Texas Southwestern Medical Center (US)
Corresponding author
Tallquist, Michelle D
Venue
PLoS Biology
Published
2003-11-17
Volume
1
Issue
2
Pages
e52
ISSN
  • 1544-9173 (ISSN-L)
  • 1545-7885
OpenAlex
W2015525302
Cited by
192
References
78
Citations by year
2026: 7 · 2025: 9 · 2024: 5 · 2023: 11 · 2022: 11 · 2021: 10 · 2020: 11 · 2019: 10 · 2018: 9 · 2017: 9 · 2016: 9 · 2015: 9 · 2014: 12 · 2013: 10 · 2012: 7
FWCI
2.07
Type
journal article
Language
en
Open access
Locations
  • PLoS Biology (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, other-oa)
  • PubMed (publishedVersion)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
Funders
  • American Cancer Society
  • American Heart Association
  • National Institute of Child Health and Human Development
  • Eunice Kennedy Shriver National Institute of Child Health and Human Development (HD-24875, HD25326, R01HD025326, R01HD024875, R37HD025326)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Protein Kinase Regulation and GTPase Signaling
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Angiogenesis and VEGF in Cancer
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › TGF-β signaling in diseases
Keywords
PDGF receptor beta, vascular smooth muscle cells, pericytes, receptor tyrosine kinase signaling, signaling pathways, Ras GTPase-activating protein, allelic series, cell development, signal attenuation
MeSH terms
Alleles, Animals, Cytoplasm, Fibroblasts, Immunohistochemistry, Kidney, Mice, Transgenic, Models, Genetic, Muscle, Smooth, Vascular, Mutation, Phenylalanine, Retina, Time Factors, Tyrosine, Blotting, Southern, Blotting, Western, Signal Transduction, Point Mutation, Protein Structure, Tertiary, Transgenes, Pericytes, Receptor Protein-Tyrosine Kinases, Receptor, Platelet-Derived Growth Factor beta, Myocytes, Smooth Muscle, Mice

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