PMID- 28943431
OWN - NLM
STAT- MEDLINE
DCOM- 20171020
LR  - 20200310
IS  - 1090-2104 (Electronic)
IS  - 0006-291X (Linking)
VI  - 493
IP  - 2
DP  - 2017 Nov 18
TI  - Src-mediated ligand release-independent EGFR transactivation involves 
      TGF-beta-induced Smad3 activation in mesangial cells.
PG  - 914-920
LID - S0006-291X(17)31892-2 [pii]
LID - 10.1016/j.bbrc.2017.09.121 [doi]
AB  - A great deal of evidence highlighted the pathophysiologic importance of 
      TGF-beta1/Smad3 pathway in masangial extracellular matrix (ECM) accumulation, but 
      some alternative signaling pathways are also involved. TGF-beta was shown recently 
      to induce rapid and transient epidermal-like growth factor receptor (EGFR) 
      transactivation and subsequent fibronectin expression via heparin-binding 
      epidermal-like growth factors (HB-EGF) release and binding in mesangial cells, 
      which is independent of Smad2 activation. However, whether TGF-beta could induce 
      persistent EGFR transactivation remains to be identified. The present study 
      demonstrates that in addition to transient EGFR transactivation, TGF-beta1 can also 
      induce continuous EGFR transactivation by a non-ligand-dependent pathway in rat 
      mesangial cells. This sustained EGFR transactivation is mainly due to Src 
      kinase-mediated persistent EGFR tyrosine phosphorylation at Y845 rather than 
      Y1173. TGF-beta1-induced early Smad3 phosphorylation is independent of transient 
      EGFR transactivation and ERK1/2 activation initiated by HB-EGF release, whereas 
      Src-mediated chronic EGFR transactivation and ERK1/2 activation participate in 
      Smad3 activation in a relatively modest and delayed manner. Therefore, the 
      present study further clarifies the mechanisms of EGFR transactivation in the 
      TGF-beta-initiated ECM upregulation and raises the possibility that targeting EGFR 
      may provide a viable alternative strategy for inhibiting TGF-beta in chronic kidney 
      disease.
CI  - Copyright (c) 2017. Published by Elsevier Inc.
FAU - Chen, Yan
AU  - Chen Y
AD  - Department of Biochemistry and Hubei Provincial Key Laboratory of Developmentally 
      Originated Disease, Wuhan University School of Basic Medical Sciences, Wuhan, PR 
      China.
FAU - Peng, Fang-Fang
AU  - Peng FF
AD  - Department of Biochemistry and Hubei Provincial Key Laboratory of Developmentally 
      Originated Disease, Wuhan University School of Basic Medical Sciences, Wuhan, PR 
      China.
FAU - Jin, Jing
AU  - Jin J
AD  - Department of Biochemistry and Hubei Provincial Key Laboratory of Developmentally 
      Originated Disease, Wuhan University School of Basic Medical Sciences, Wuhan, PR 
      China.
FAU - Chen, Hong-Min
AU  - Chen HM
AD  - Department of Biochemistry and Hubei Provincial Key Laboratory of Developmentally 
      Originated Disease, Wuhan University School of Basic Medical Sciences, Wuhan, PR 
      China.
FAU - Yu, Hong
AU  - Yu H
AD  - Department of Biochemistry and Hubei Provincial Key Laboratory of Developmentally 
      Originated Disease, Wuhan University School of Basic Medical Sciences, Wuhan, PR 
      China.
FAU - Zhang, Bai-Fang
AU  - Zhang BF
AD  - Department of Biochemistry and Hubei Provincial Key Laboratory of Developmentally 
      Originated Disease, Wuhan University School of Basic Medical Sciences, Wuhan, PR 
      China. Electronic address: zbfwq@whu.edu.cn.
LA  - eng
PT  - Journal Article
DEP - 20170922
PL  - United States
TA  - Biochem Biophys Res Commun
JT  - Biochemical and biophysical research communications
JID - 0372516
RN  - 0 (Smad3 Protein)
RN  - 0 (Smad3 protein, rat)
RN  - 0 (Transforming Growth Factor beta)
RN  - EC 2.7.10.1 (ErbB Receptors)
RN  - EC 2.7.10.2 (CSK Tyrosine-Protein Kinase)
RN  - EC 2.7.10.2 (src-Family Kinases)
RN  - EC 2.7.11.24 (Mitogen-Activated Protein Kinase 1)
RN  - EC 2.7.11.24 (Mitogen-Activated Protein Kinase 3)
SB  - IM
MH  - Animals
MH  - CSK Tyrosine-Protein Kinase
MH  - Cells, Cultured
MH  - ErbB Receptors/*genetics/metabolism
MH  - Mesangial Cells/*metabolism
MH  - Mitogen-Activated Protein Kinase 1/metabolism
MH  - Mitogen-Activated Protein Kinase 3/metabolism
MH  - Phosphorylation
MH  - Rats, Sprague-Dawley
MH  - Smad3 Protein/*metabolism
MH  - *Transcriptional Activation
MH  - Transforming Growth Factor beta/*metabolism
MH  - src-Family Kinases/*metabolism
OTO - NOTNLM
OT  - EGFR
OT  - Fibronectin
OT  - Src
OT  - TGF-beta
EDAT- 2017/09/26 06:00
MHDA- 2017/10/21 06:00
CRDT- 2017/09/26 06:00
PHST- 2017/09/11 00:00 [received]
PHST- 2017/09/21 00:00 [accepted]
PHST- 2017/09/26 06:00 [pubmed]
PHST- 2017/10/21 06:00 [medline]
PHST- 2017/09/26 06:00 [entrez]
AID - S0006-291X(17)31892-2 [pii]
AID - 10.1016/j.bbrc.2017.09.121 [doi]
PST - ppublish
SO  - Biochem Biophys Res Commun. 2017 Nov 18;493(2):914-920. doi: 
      10.1016/j.bbrc.2017.09.121. Epub 2017 Sep 22.