IDEAS home Printed from https://ideas.repec.org/a/nat/natcom/v8y2017i1d10.1038_s41467-017-01168-1.html
   My bibliography  Save this article

PTP4A1 promotes TGFβ signaling and fibrosis in systemic sclerosis

Author

Listed:
  • Cristiano Sacchetti

    (University of California San Diego
    La Jolla Institute for Allergy and Immunology)

  • Yunpeng Bai

    (Purdue University)

  • Stephanie M. Stanford

    (University of California San Diego
    La Jolla Institute for Allergy and Immunology)

  • Paola Di Benedetto

    (University of L’Aquila)

  • Paola Cipriani

    (University of L’Aquila)

  • Eugenio Santelli

    (University of California San Diego
    La Jolla Institute for Allergy and Immunology)

  • Sonsoles Piera-Velazquez

    (Scleroderma Center and Jefferson Institute of Molecular Medicine)

  • Vladimir Chernitskiy

    (University of California San Francisco)

  • William B. Kiosses

    (The Scripps Research Institute)

  • Arnold Ceponis

    (University of California San Diego)

  • Klaus H. Kaestner

    (University of Pennsylvania)

  • Francesco Boin

    (University of California San Francisco)

  • Sergio A. Jimenez

    (Scleroderma Center and Jefferson Institute of Molecular Medicine)

  • Roberto Giacomelli

    (University of L’Aquila)

  • Zhong-Yin Zhang

    (Purdue University)

  • Nunzio Bottini

    (University of California San Diego
    La Jolla Institute for Allergy and Immunology)

Abstract

Systemic sclerosis (SSc) is an autoimmune disease characterized by fibrosis of skin and internal organs. Protein tyrosine phosphatases have received little attention in the study of SSc or fibrosis. Here, we show that the tyrosine phosphatase PTP4A1 is highly expressed in fibroblasts from patients with SSc. PTP4A1 and its close homolog PTP4A2 are critical promoters of TGFβ signaling in primary dermal fibroblasts and of bleomycin-induced fibrosis in vivo. PTP4A1 promotes TGFβ signaling in human fibroblasts through enhancement of ERK activity, which stimulates SMAD3 expression and nuclear translocation. Upstream from ERK, we show that PTP4A1 directly interacts with SRC and inhibits SRC basal activation independently of its phosphatase activity. Unexpectedly, PTP4A2 minimally interacts with SRC and does not promote the SRC–ERK–SMAD3 pathway. Thus, in addition to defining PTP4A1 as a molecule of interest for TGFβ-dependent fibrosis, our study provides information regarding the functional specificity of different members of the PTP4A subclass of phosphatases.

Suggested Citation

  • Cristiano Sacchetti & Yunpeng Bai & Stephanie M. Stanford & Paola Di Benedetto & Paola Cipriani & Eugenio Santelli & Sonsoles Piera-Velazquez & Vladimir Chernitskiy & William B. Kiosses & Arnold Cepon, 2017. "PTP4A1 promotes TGFβ signaling and fibrosis in systemic sclerosis," Nature Communications, Nature, vol. 8(1), pages 1-14, December.
    • Handle: RePEc:nat:natcom:v:8:y:2017:i:1:d:10.1038_s41467-017-01168-1
    DOI: 10.1038/s41467-017-01168-1
    as

    Download full text from publisher

    File URL: https://www.nature.com/articles/s41467-017-01168-1
    File Function: Abstract
    Download Restriction: no
    File URL: https://libkey.io/10.1038/s41467-017-01168-1?utm_source=ideas
    LibKey link: if access is restricted and if your library uses this service, LibKey will redirect you to where you can use your library subscription to access this item
    ---><---

    More about this item

    Statistics

    Access and download statistics

    Corrections

    All material on this site has been provided by the respective publishers and authors. You can help correct errors and omissions. When requesting a correction, please mention this item's handle: RePEc:nat:natcom:v:8:y:2017:i:1:d:10.1038_s41467-017-01168-1. See general information about how to correct material in RePEc.

    If you have authored this item and are not yet registered with RePEc, we encourage you to do it here. This allows to link your profile to this item. It also allows you to accept potential citations to this item that we are uncertain about.

    We have no bibliographic references for this item. You can help adding them by using this form .

    If you know of missing items citing this one, you can help us creating those links by adding the relevant references in the same way as above, for each refering item. If you are a registered author of this item, you may also want to check the "citations" tab in your RePEc Author Service profile, as there may be some citations waiting for confirmation.

    For technical questions regarding this item, or to correct its authors, title, abstract, bibliographic or download information, contact: Sonal Shukla or Springer Nature Abstracting and Indexing (email available below). General contact details of provider: http://www.nature.com .

    Please note that corrections may take a couple of weeks to filter through the various RePEc services.

    IDEAS is a RePEc service. RePEc uses bibliographic data supplied by the respective publishers.