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STATs as critical mediators of signal transduction and transcription: lessons learned from STAT5
- Source :
- Cytokine & Growth Factor Reviews. 15:435-455
- Publication Year :
- 2004
- Publisher :
- Elsevier BV, 2004.
-
Abstract
- Signal transducers and activators of transcription (Stats) comprise a family of seven transcription factors that are activated by a variety of cytokines, hormones and growth factors. Stats are activated through tyrosine phosphorylation, mainly by Jak kinases, that lead to their dimerization, nuclear translocation and regulation of target gene expression. Stat5 was originally identified as a transcription factor that regulates the beta-casein gene in response to prolactin (PRL), but Stat5 is activated also by several other cytokines and growth factors. The molecular mechanisms that underlie Stat5-mediated transcription involve interactions and cooperation with sequence specific transcription factors and transcriptional coregulators. Our studies identified p100 protein as a coactivator for Stat5, and suggest the existence of a positive regulatory loop in PRL-induced transcription, where PRL stabilizes p100 protein, which in turn can cooperate with Stat5 in transcriptional activation. Suppressors of cytokine signaling (SOCS) proteins are important negative regulators of Stats. A target gene for Stat5, the serine/threonine kinase Pim-1, was found to cooperate with SOCS-1 and SOCS-3 to inhibit Stat5 activity suggesting that Pim-1 together with SOCS-1 and SOCS-3 are components of a negative feedback mechanism that allows Stat5 to regulate its own activation.
- Subjects :
- Transcription, Genetic
Protein Conformation
Endocrinology, Diabetes and Metabolism
Immunology
Response element
Receptors, Cell Surface
E-box
Transcription coregulator
Protein Serine-Threonine Kinases
Biology
General Biochemistry, Genetics and Molecular Biology
03 medical and health sciences
Proto-Oncogene Proteins c-pim-1
Sp3 transcription factor
GTP-Binding Proteins
Proto-Oncogene Proteins
hemic and lymphatic diseases
STAT5 Transcription Factor
Animals
Immunology and Allergy
Protein inhibitor of activated STAT
Growth Substances
Transcription factor
030304 developmental biology
0303 health sciences
General transcription factor
030302 biochemistry & molecular biology
Nuclear Proteins
food and beverages
Protein-Tyrosine Kinases
Milk Proteins
DNA-Binding Proteins
Gene Expression Regulation
TAF2
Trans-Activators
Cancer research
Cytokines
Signal Transduction
Subjects
Details
- ISSN :
- 13596101
- Volume :
- 15
- Database :
- OpenAIRE
- Journal :
- Cytokine & Growth Factor Reviews
- Accession number :
- edsair.doi.dedup.....0313db4462559db5e347a09c0b80d455