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Investigating py‐STAT6 protein levels and mRNA expression of STAT6 regulated genes in renal epithelial cells (1180.8)
Author(s) -
Boslett Brianna,
Resnick Andrew
Publication year - 2014
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.28.1_supplement.1180.8
Subject(s) - stat6 , gene , biology , transcription factor , stat , microbiology and biotechnology , transcription (linguistics) , gene expression , genetics , stat3 , linguistics , philosophy
The current study will investigate the mechanosensory‐signaling pathway leading to STAT6 gene transcription in mouse cortical collecting duct epithelial cells. Many stimulants are capable of activating STAT6 in the kidney, but it is still unknown how STAT6 is directed to specific gene targets. In several cases, transcription co‐factors, such as a fragment of polycystin 1, have been found to enter the nucleus along with STAT6 dimers. Additionally, the mechanism by which STAT6 becomes activated by mechanosensation is currently unknown. A primary goal of this study is to determine the kinase involved in STAT6 phosphorylation (activation) in changing flow conditions. The STAT family has cell‐type specific promoter binding sites. Common STAT controlled cis‐regulatory modules (cSCCs) are cis‐regulatory modules (CRMs) that can be recognized by all STAT family members across cell types. 116 cSCCs have been identified and correspond to JAK/STAT signaling genes. I hypothesize that different stimulants (cytokines vs. fluid flow) will lead STAT6 to transcribe different genes. Therefore, STAT6 binding sites that do not correspond to cSCCs will be investigated for cell specific, or stimuli‐specific STAT6 gene transcription. These results will have implications for ADPKD, which is caused by genetic mutations leading to defects in polycystin 1 (PC1) and polycystin 2 (PC2) proteins. Grant Funding Source : Supported by the National Institute of Diabetes and Digestive and Kidney Diseases 1R15DK092716