skip to main content
OSTI.GOV title logo U.S. Department of Energy
Office of Scientific and Technical Information

Title: Role played by Disabled-2 in albumin induced MAP Kinase signalling

Abstract

Albumin has been shown to activate the mitogen activated protein kinase (MAPK) pathway in proximal tubular cells (PTECs) of the kidney. Megalin, the putative receptor for albumin has potential signalling properties. However, the mechanisms by which megalin signals are unclear. The adaptor phosphoprotein Disabled-2 (Dab2) is known to interact with the cytoplasmic tail of megalin and may be involved in albumin-mediated MAPK signalling. In this study, we investigated the role of Dab2 in albumin-mediated MAPK signalling and further studied the role of Dab2 in albumin-induced TGF{beta}-1 secretion, a MAPK dependent event. We used RNA interference to knockdown Dab2 protein abundance in HKC-8 cells a model of human PTECs. Albumin activated ERK1,2 and Elk-1 in a MEK-1 dependent manner and resulted in secretion of TGF{beta}-1. In the absence of albumin, knockdown of Dab2 resulted in a trend towards increase in pERK1,2 consistent with its putative role as an inhibitor of cell proliferation. However albumin-induced ERK1,2 activation was completely abolished by Dab2 knockdown. Dab2 knockdown did not however result in inhibition of albumin-induced TGF{beta}-1 secretion. These results suggest that Dab2 is a ligand dependent bi-directional regulator of ERK1,2 activity by demonstrating that in addition to its more traditional role as an inhibitormore » of ERK1,2 it may also activate ERK1,2.« less

Authors:
 [1]; ;  [1];  [2];  [1]
  1. South West Thames Institute for Renal Research, St. Helier Hospital, Wrythe Lane, Carshalton, Surrey SM5 1AA (United Kingdom)
  2. Basic Medical Sciences, St. Georges University of London, Cranmer Terrace, Tooting, London (United Kingdom)
Publication Date:
OSTI Identifier:
21043622
Resource Type:
Journal Article
Journal Name:
Biochemical and Biophysical Research Communications
Additional Journal Information:
Journal Volume: 366; Journal Issue: 3; Other Information: DOI: 10.1016/j.bbrc.2007.11.171; PII: S0006-291X(07)02583-1; Copyright (c) 2007 Elsevier Science B.V., Amsterdam, The Netherlands, All rights reserved; Country of input: International Atomic Energy Agency (IAEA); Journal ID: ISSN 0006-291X
Country of Publication:
United States
Language:
English
Subject:
60 APPLIED LIFE SCIENCES; ALBUMINS; CELL PROLIFERATION; INHIBITION; KIDNEYS; LIGANDS; PHOSPHOPROTEINS; RECEPTORS; RNA; SECRETION

Citation Formats

Diwakar, Ramaswamy, Pearson, Alexander L, Colville-Nash, Paul, Baines, Deborah L, and Dockrell, Mark E.C. Role played by Disabled-2 in albumin induced MAP Kinase signalling. United States: N. p., 2008. Web. doi:10.1016/j.bbrc.2007.11.171.
Diwakar, Ramaswamy, Pearson, Alexander L, Colville-Nash, Paul, Baines, Deborah L, & Dockrell, Mark E.C. Role played by Disabled-2 in albumin induced MAP Kinase signalling. United States. https://doi.org/10.1016/j.bbrc.2007.11.171
Diwakar, Ramaswamy, Pearson, Alexander L, Colville-Nash, Paul, Baines, Deborah L, and Dockrell, Mark E.C. 2008. "Role played by Disabled-2 in albumin induced MAP Kinase signalling". United States. https://doi.org/10.1016/j.bbrc.2007.11.171.
@article{osti_21043622,
title = {Role played by Disabled-2 in albumin induced MAP Kinase signalling},
author = {Diwakar, Ramaswamy and Pearson, Alexander L and Colville-Nash, Paul and Baines, Deborah L and Dockrell, Mark E.C.},
abstractNote = {Albumin has been shown to activate the mitogen activated protein kinase (MAPK) pathway in proximal tubular cells (PTECs) of the kidney. Megalin, the putative receptor for albumin has potential signalling properties. However, the mechanisms by which megalin signals are unclear. The adaptor phosphoprotein Disabled-2 (Dab2) is known to interact with the cytoplasmic tail of megalin and may be involved in albumin-mediated MAPK signalling. In this study, we investigated the role of Dab2 in albumin-mediated MAPK signalling and further studied the role of Dab2 in albumin-induced TGF{beta}-1 secretion, a MAPK dependent event. We used RNA interference to knockdown Dab2 protein abundance in HKC-8 cells a model of human PTECs. Albumin activated ERK1,2 and Elk-1 in a MEK-1 dependent manner and resulted in secretion of TGF{beta}-1. In the absence of albumin, knockdown of Dab2 resulted in a trend towards increase in pERK1,2 consistent with its putative role as an inhibitor of cell proliferation. However albumin-induced ERK1,2 activation was completely abolished by Dab2 knockdown. Dab2 knockdown did not however result in inhibition of albumin-induced TGF{beta}-1 secretion. These results suggest that Dab2 is a ligand dependent bi-directional regulator of ERK1,2 activity by demonstrating that in addition to its more traditional role as an inhibitor of ERK1,2 it may also activate ERK1,2.},
doi = {10.1016/j.bbrc.2007.11.171},
url = {https://www.osti.gov/biblio/21043622}, journal = {Biochemical and Biophysical Research Communications},
issn = {0006-291X},
number = 3,
volume = 366,
place = {United States},
year = {Fri Feb 15 00:00:00 EST 2008},
month = {Fri Feb 15 00:00:00 EST 2008}
}