IMR Press / FBL / Volume 16 / Issue 8 / DOI: 10.2741/3897

Frontiers in Bioscience-Landmark (FBL) is published by IMR Press from Volume 26 Issue 5 (2021). Previous articles were published by another publisher on a subscription basis, and they are hosted by IMR Press on as a courtesy and upon agreement with Frontiers in Bioscience.

Open Access Article
Serine phosphorylation of the Stat5a C-terminus is a driving force for transformation
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1 Ludwig Boltzmann Institute for Cancer Research (LBI-CR), Vienna, Austria
2 Institute of Pharmacology, Medical University of Vienna, Vienna, Austria
3 Deptartment of Pediatrics, Division of Hem-Onc, Boston Children’s Hospital, Boston Massachusetts, USA
4 Department of Pediatrics, Division of Hem-Onc-BMT and Aflac Cancer Center and Blood Disorders Service, Emory University, 2015 Uppergate Dr. NE, Atlanta, Georgia 30322, USA
5 Centre National de la Recherche Scientifique (CNRS) UMR 6239, Universite F. Rabelais, UFR Medecine, Tours, France
Academic Editor:Serge Haan
Front. Biosci. (Landmark Ed) 2011, 16(8), 3043–3056;
Published: 1 June 2011
(This article belongs to the Special Issue Regulation of signalling in health and disease)

Persistent tyrosine phosphorylation of Stat3 and Stat5 is associated with oncogenic activity. Phosphorylation of the conserved tyrosine residue (pTyr) was long believed to be the only essential prerequisite to promote activation and nuclear translocation of Stat proteins. It has become evident, however, that post-translational protein modifications like serine phosphorylation, acetylation, glycosylation as well as protein splicing and processing constitute further regulatory mechanisms to modulate Stat transcriptional activity and to provide an additional layer of specificity to Jak-Stat signal transduction. Significantly, most vertebrate Stat proteins contain one conserved serine phosphorylation site within their transactivation domains. This phosphorylation motif is located within a P(M)SP sequence. Stat transcription factor activity is negatively influenced by mutation of the serine to alanine. Moreover, it was shown for both Stat3 and Stat5 that their capacity to transform cells was diminished. This review addresses recent advances in understanding the regulation and the biochemical and biological consequences of Stat serine phosphorylation. In particular, we discuss their role in persistently activated Stat proteins for cancer research.

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