+ Site Statistics
+ Search Articles
+ PDF Full Text Service
How our service works
Request PDF Full Text
+ Follow Us
Follow on Facebook
Follow on Twitter
Follow on LinkedIn
+ Subscribe to Site Feeds
Most Shared
PDF Full Text
+ Translate
+ Recently Requested

Essential role of STAT3 in postnatal survival and growth revealed by mice lacking STAT3 serine 727 phosphorylation



Essential role of STAT3 in postnatal survival and growth revealed by mice lacking STAT3 serine 727 phosphorylation



Molecular and Cellular Biology 24(1): 407-419



A large number of extracellular polypeptides bound to their cognate receptors activate the transcription factor STAT3 by phosphorylation of tyrosine 705. Supplemental activation occurs when serine 727 is also phosphorylated. STAT3 deletion in mice leads to embryonic lethality. We have produced mice with alanine substituted for serine 727 in STAT3 (the SA allele) to examine the function of serine 727 phosphorylation in vivo. Embryonic fibroblasts from SA/SA mice had approximately 50% of the transcriptional response of wild-type cells. However, SA/SA mice were viable and grossly normal. STAT3 wild-type/null (+/-) animals were also normal and were interbred with SA/SA mice to study SA/- mice. The SA/- mice progressed through gestation, showing 10 to 15% reduced birth weight, three-fourths died soon after birth, and the SA/- survivors reached only 50 to 60% of normal size at 1 week of age. The lethality and decreased growth were accompanied by altered insulin-like growth factor 1 (IGF-1) levels in serum, establishing a role for the STAT3 serine phosphorylation acting through IGF-1 in embryonic and perinatal growth. The SA/- survivors have decreased thymocyte number associated with increased apoptosis, but unexpectedly normal STAT3-dependent liver acute phase response. These animals offer the opportunity to study defined reductions in the transcriptional capacity of a widely used signaling pathway.

Please choose payment method:






(PDF emailed within 1 workday: $29.90)

Accession: 048979757

Download citation: RISBibTeXText

PMID: 14673173


Related references

Essential Role of Stat3 in Postnatal Survival and Growth Revealed by Mice Lacking Stat3 Serine 727 Phosphorylation. Molecular and Cellular Biology 24(1): 407-419, 2004

Role of STAT3 in angiotensin II-induced hypertension and cardiac remodeling revealed by mice lacking STAT3 serine 727 phosphorylation. Hypertension Research 36(6): 496-503, 2013

Serine phosphorylation of STAT3 is essential for Mcl-1 expression and macrophage survival. Blood 102(1): 344-352, 2003

Mapping of Stat3 serine phosphorylation to a single residue (727) and evidence that serine phosphorylation has no influence on DNA binding of Stat1 and Stat3. Nucleic Acids Research 25(11): 2062-2067, 1997

Eriocalyxin B Inhibits STAT3 Signaling by Covalently Targeting STAT3 and Blocking Phosphorylation and Activation of STAT3. Plos One 10(5): E0128406, 2016

Nuclear translocation of phosphorylated STAT3 is essential for endothelial cell migration induced by basic FGF STAT3 phosphorylation is involved in tube formation. Journal of Investigative Dermatology 117(2): 390, 2001

DNA-binding activity of STAT3 increased in hypothalamus of DIO mice; the reduction of STAT3 phosphorylation may facilitate leptin signaling. Biochemical and Biophysical Research Communications 505(1): 229-235, 2018

Electrochemical detection of the Fc-STAT3 phosphorylation and STAT3-Fc-STAT3 dimerization and inhibition. Molecular Biosystems 10(3): 576-580, 2014

STAT3 phosphorylation in injured axons before sensory and motor neuron nuclei: potential role for STAT3 as a retrograde signaling transcription factor. Journal of Comparative Neurology 474(4): 535-545, 2004

Mitochondrial localized Stat3 promotes breast cancer growth via phosphorylation of serine 727. Journal of Biological Chemistry 288(43): 31280-8, 2014

Crucial role of STAT3 for angiogenesis, contractility and protection against ischemia Evidence from mice with cardiomyocyte specific knock out of STAT3. Circulation 106(19 Suppl.): II-258, November 5, 2002

Serine phosphorylation of Stat1 and Stat3 is induced by treatment of cells with UV radiation Potential role of p38 MAPK. Journal of Interferon & Cytokine Research 19(SUPPL 1): S66, Sept, 1999

STAT3 complements defects in an interferon-resistant cell line: Evidence for an essential role for STAT3 in interferon signaling and biological activities. Proceedings of the National Academy of Sciences of the United States of America 95(10): 5568-5572, 1998

Identification of two Stat3 variants lacking a transactivation domain in grass carp: New insights into alternative splicing in the modification of teleost Stat3 signaling. Fish and Shellfish Immunology 77: 13-21, 2018

Identification of two Stat3 variants lacking a transactivation domain in grass carp: New insights into alternative splicing in the modification of teleost Stat3 signaling. Fish & Shellfish Immunology 77: 13-21, 2018