Faculty Collaboration Database

Endothelin-1 induces serine phosphorylation of the adaptor protein p66Shc and its association with 14-3-3 protein in glomerular mesangial cells. J Biol Chem 2001 Jul 13;276(28):26640-7

Date

05/09/2001

Pubmed ID

11342545

DOI

10.1074/jbc.M102008200

Scopus ID

2-s2.0-0035854682 (requires institutional sign-in at Scopus site)   41 Citations

Abstract

Endothelin-1 (ET-1) is a vasoconstrictor peptide known to be a potent mitogen for glomerular mesangial cells (GMC). In the current study, it is demonstrated that ET-1 treatment of GMC results in serine phosphorylation of the 66-kDa isoform of the adapter protein Shc (p66(Shc)). ET-1-induced serine phosphorylation of p66(Shc) requires activation of the mitogen-activated protein kinase (MAPK)/extracellular signal-regulated kinase (ERK) signaling module and is efficiently inhibited by both a MAPK/ERK kinase (MEK)-selective inhibitor and adenovirus-mediated transfer of a dominant interfering MEK1 mutant. Furthermore, adenovirus-mediated transfer of a constitutively active MEK1 mutant was found to markedly increase p66(Shc) serine phosphorylation. Adenoviruses encoding constitutively active mutants of MAPK kinases 3 and 6 (upstream kinases of p38(MAPK)) and 7 (upstream kinase of c-Jun NH(2)-terminal kinase) failed to induce serine phosphorylation of this adaptor protein. Serine phosphorylation of p66(Shc) resulted in its association with the serine binding motif-containing protein 14-3-3. ET-1-induced phosphorylation of a serine encompassed in the 14-3-3 binding motif of p66(Shc) was confirmed in experiments employing anti-phospho-14-3-3 binding motif antibodies. These studies are the first to demonstrate that G protein-coupled receptors stimulate serine phosphorylation of p66(Shc) and the first to report the formation of a signaling complex between p66(Shc) and 14-3-3.

Author List

Foschi M, Franchi F, Han J, La Villa G, Sorokin A

Author

Andrey Sorokin PhD Professor in the Medicine department at Medical College of Wisconsin

MESH terms used to index this publication - Major topics in bold

14-3-3 Proteins
Adaptor Proteins, Signal Transducing
Adaptor Proteins, Vesicular Transport
Animals
Cells, Cultured
Endothelin-1
Glomerular Mesangium
Humans
Phosphorylation
Proteins
Rats
Rats, Sprague-Dawley
Serine
Shc Signaling Adaptor Proteins
Signal Transduction
Src Homology 2 Domain-Containing, Transforming Protein 1
Tyrosine 3-Monooxygenase