Phosphorylation of alpha-actinin 4 upon epidermal growth factor exposure regulates its interaction with actin.

The Journal of Biological Chemistry
Hanshuang ShaoAlan Wells

Abstract

The ubiquitously expressed family of alpha-actinins bridges actin filaments to stabilize adhesions, a process disrupted during growth factor-induced migration of cells. During the dissolution of the actin cytoskeleton, actinins are phosphorylated on tyrosines, although the consequences of this are unknown. We expressed the two isoforms of human alpha-actinin in murine fibroblasts that express human epidermal growth factor receptor (EGFR) and found that both alpha-actinin 1 (ACTN1) and alpha-actinin 4 (ACTN4) were phosphorylated on tyrosine residues after stimulation with EGF, although ACTN4 was phosphorylated to the greater extent. This required the activation of Src protein-tyrosine kinase and p38-MAPK (and phosphoinositide trisphosphate kinase in part) but not MEK/ERK or Rac1, as determined by inhibitors. The EGF-induced phosphorylation sites of ACTN4 were mapped to tyrosine 4, the major site, and tyrosine 31, the minor one. Truncation mutagenesis showed that the C-terminal domains of ACTN4 (amino acids 300-911), which cross-link the actin binding head domains, act as an inhibitory domain for both actin binding and EGF-mediated phosphorylation. These two properties were mutually exclusive; removal of the C terminus enhanced a...Continue Reading

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Citations

Mar 8, 2013·The International Journal of Biochemistry & Cell Biology·Hanshuang ShaoAlan Wells
May 13, 2010·Journal of Proteome Research·Brian L HoodThomas P Conrads
Jun 21, 2013·Open Biology·Tea Vallenius
May 10, 2012·PLoS Biology·Tomas Garzon-MuvdiAlfredo Quiñones-Hinojosa
Aug 1, 2012·Journal of Signal Transduction·Cristina BertocchiRonen Zaidel-Bar
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Feb 28, 2013·Biophysical Journal·Timothy TraversCarlos J Camacho
Mar 28, 2017·Journal of the Science of Food and Agriculture·Xin LiDequan Zhang
Dec 25, 2016·Biochemical and Biophysical Research Communications·Kyoung Ryoung ParkSoo Hyun Eom
May 1, 2018·Oncogene·Yuan Yuan ZhangLei Jin
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Jul 21, 2020·American Journal of Physiology. Renal Physiology·Di Feng
Oct 10, 2014·The Journal of Biological Chemistry·Hanshuang ShaoAlan Wells
Jun 17, 2020·Journal of the American Society of Nephrology : JASN·Di FengMartin R Pollak
Nov 12, 2020·Biology·Jaya Aseervatham
Feb 13, 2021·International Journal of Molecular Sciences·Korinn N Murphy, Amanda J Brinkworth
Dec 24, 2017·The International Journal of Biochemistry & Cell Biology·Hanshuang ShaoAlan Wells
Aug 2, 2020·Molecular Aspects of Medicine·Yi Zhu, Gerald W Hart
Jan 18, 2021·Biochimica Et Biophysica Acta. Molecular Cell Research·Daisuke SaitoNoriko Takahashi
May 1, 2021·International Journal of Molecular Sciences·Alexey ShalyginElena Kaznacheyeva
Oct 8, 2021·Journal of Cellular Physiology·Vasiliki-Dimitra C TsolakiAsterios S Tsiftsoglou

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