Identification and characterization of a constitutively active STAT5 mutant that promotes cell proliferation.

Molecular and Cellular Biology
M OnishiT Kitamura

Abstract

STAT (signal transducers and activators of transcription) proteins are transcription factors which are activated by phosphorylation on tyrosine residues upon stimulation by cytokines. Seven members of the STAT family are known, including the closely related STAT5A and STAT5B, which are activated by various cytokines. Except for prolactin-dependent beta-casein production in mammary gland cells, the biological consequences of STAT5 activation in various systems are not clear. We applied PCR-driven random mutagenesis and a retrovirus-mediated expression screening system to identify constitutively active forms of STAT5. By this strategy, we have identified a constitutively active STAT5 mutant which has two amino acid substitutions; one is located upstream of the putative DNA binding domain (H299R), and the other is located in the transactivation domain (S711F). The mutant STAT5 was constitutively phosphorylated on tyrosine residues, localized in the nucleus, and was transcriptionally active. Expression of the mutant STAT5 partially dispenses with interleukin 3 (IL-3) as a growth stimulant of IL-3-dependent cell lines. Further analyses of the mutant STAT5 have demonstrated that both of the mutations are required for nuclear localiza...Continue Reading

References

May 17, 1995·Journal of the National Cancer Institute·C K OsborneR I Nicholson
Sep 12, 1995·Proceedings of the National Academy of Sciences of the United States of America·X LiuL Hennighausen
Sep 26, 1995·Proceedings of the National Academy of Sciences of the United States of America·T KitamuraG P Nolan
Sep 29, 1995·Science·N N DanialP B Rothman
Jan 1, 1995·Annual Review of Biochemistry·C Schindler, J E Darnell
Sep 15, 1993·Proceedings of the National Academy of Sciences of the United States of America·W S PearD Baltimore
Sep 16, 1994·Science·J HouS L McKnight
Apr 1, 1996·Molecular and Cellular Biology·X CaoY H Tan
Mar 5, 1996·Proceedings of the National Academy of Sciences of the United States of America·M C FriedmannW J Leonard
Nov 1, 1996·Molecular and Cellular Biology·D WangJ N Ihle
Jan 15, 1997·Genes & Development·X LiuL Hennighausen
Feb 21, 1997·The Journal of Biological Chemistry·R J RayanadeP B Sehgal
Apr 15, 1997·Proceedings of the National Academy of Sciences of the United States of America·Y KawakamiT Kawakami
Jul 8, 1997·Proceedings of the National Academy of Sciences of the United States of America·G B UdyH W Davey
Jan 13, 1998·Biochimica Et Biophysica Acta·A B RaitanoC L Sawyers

❮ Previous
Next ❯

Citations

Feb 22, 2012·Expert Opinion on Therapeutic Targets·Mamatha M ReddyMartin Sattler
Feb 22, 2012·Growth Factors·Hiu Kiu, Sandra E Nicholson
Jan 6, 2006·Growth Factors·Evan Ingley, S Peter Klinken
May 26, 2010·The Journal of Experimental Medicine·Cihangir DuyMarkus Müschen
Jan 25, 2012·The Journal of Experimental Medicine·Robert J JohnstonShane Crotty
Dec 31, 2015·Journal of Interferon & Cytokine Research : the Official Journal of the International Society for Interferon and Cytokine Research·Aradhana Rani, John J Murphy
May 25, 2010·Microbes and Infection·Xianfeng ZhangHisatoshi Shida
Feb 23, 2008·Trends in Biochemical Sciences·Stefan N ConstantinescuChristian Pecquet
Nov 6, 2007·Analytical Biochemistry·Tsuguto TodaKoichi Ikuta
May 18, 2001·Cytokine·S L Gaffen
Sep 14, 2011·British Journal of Haematology·Huiyuan LiRenchi Yang
Nov 25, 2004·Cytokine & Growth Factor Reviews·Kirsi Paukku, Olli Silvennoinen
Sep 11, 2004·Biochemical and Biophysical Research Communications·Hiroki SasanumaRyo Goitsuka
Feb 8, 2006·Biochemical and Biophysical Research Communications·Natsuko TanimuraKensuke Miyake
Nov 24, 2005·Seminars in Immunology·Craig D Milne, Christopher J Paige
Oct 19, 2010·The American Journal of Pathology·Kevin J JohnsonHallgeir Rui
May 7, 2016·Growth Hormone & IGF Research : Official Journal of the Growth Hormone Research Society and the International IGF Research Society·Kumi FutawakaKenji Moriyama
Sep 5, 2007·Cytokine·Christina Kittipatarin, Annette R Khaled
Nov 15, 2003·Immunity·Jinfang ZhuWilliam E Paul
Sep 20, 2005·Current Biology : CB·Claudia WellbrockManfred Schartl
Aug 24, 1999·Cell·J F BrombergJ E Darnell
Aug 1, 2007·Molecular Immunology·Naomi MasuiKoichi Ikuta
Jan 18, 2005·Cancer Cell·Richard MorigglHartmut Beug
Jun 18, 2011·Biochemical and Biophysical Research Communications·Louise T DalgaardJens H Nielsen

❮ Previous
Next ❯

Related Concepts

Trending Feeds

COVID-19

Coronaviruses encompass a large family of viruses that cause the common cold as well as more serious diseases, such as the ongoing outbreak of coronavirus disease 2019 (COVID-19; formally known as 2019-nCoV). Coronaviruses can spread from animals to humans; symptoms include fever, cough, shortness of breath, and breathing difficulties; in more severe cases, infection can lead to death. This feed covers recent research on COVID-19.

Blastomycosis

Blastomycosis fungal infections spread through inhaling Blastomyces dermatitidis spores. Discover the latest research on blastomycosis fungal infections here.

Nuclear Pore Complex in ALS/FTD

Alterations in nucleocytoplasmic transport, controlled by the nuclear pore complex, may be involved in the pathomechanism underlying multiple neurodegenerative diseases including Amyotrophic Lateral Sclerosis and Frontotemporal Dementia. Here is the latest research on the nuclear pore complex in ALS and FTD.

Applications of Molecular Barcoding

The concept of molecular barcoding is that each original DNA or RNA molecule is attached to a unique sequence barcode. Sequence reads having different barcodes represent different original molecules, while sequence reads having the same barcode are results of PCR duplication from one original molecule. Discover the latest research on molecular barcoding here.

Chronic Fatigue Syndrome

Chronic fatigue syndrome is a disease characterized by unexplained disabling fatigue; the pathology of which is incompletely understood. Discover the latest research on chronic fatigue syndrome here.

Evolution of Pluripotency

Pluripotency refers to the ability of a cell to develop into three primary germ cell layers of the embryo. This feed focuses on the mechanisms that underlie the evolution of pluripotency. Here is the latest research.

Position Effect Variegation

Position Effect Variagation occurs when a gene is inactivated due to its positioning near heterochromatic regions within a chromosome. Discover the latest research on Position Effect Variagation here.

STING Receptor Agonists

Stimulator of IFN genes (STING) are a group of transmembrane proteins that are involved in the induction of type I interferon that is important in the innate immune response. The stimulation of STING has been an active area of research in the treatment of cancer and infectious diseases. Here is the latest research on STING receptor agonists.

Microbicide

Microbicides are products that can be applied to vaginal or rectal mucosal surfaces with the goal of preventing, or at least significantly reducing, the transmission of sexually transmitted infections. Here is the latest research on microbicides.