STATs transcription

PIAS (protein inhibitors of activated STATs) proteins were first discovered in yeast-two-hybrid screens as interacting molecules with STAT transcription factors. The mammalian family consists ofthe founding member PIAS3, which was described as a repressor of STAT3, and three additional members, PIAS1, PIASy (also known as PIAS4), and PIASx (also known as... 

FIGURE 4.3 Growth hormone receptor. Monomeric GH associates with two receptor monomers. Activated JAK2 kinases /ram-phosphorylatc JAK2 and GH receptors, and STAT transcription factors are phosphorylated by JAK2. 

Levy DE, Darnell JE, Jr. (2002). Stats transcriptional control and biological impact. Nat Rev Mol Cell Biol 3 651-662. 

The receptors for cytokines and interferons are the starting point for signal transduction chains that bring about an activation of transcription factors. The signaling pathway involves the Janus protein kinase and Stat transcription factors (see 11.1.4). Phosphoty-rosine-SH2 interactions are also involved in several steps of signal transduction here. 

Fig. 10.5a). Differences in the length of spacers between TT and AA in the GAS-element are thought to be responsible for discrimination between different STAT transcription factors. Interferon-cc/p signals are transmitted through heterodimeric STAT 1/STAT 2, which form a complex with a protein, p48, and recruit ISGF3 (the interferon-stimulated gene factor 3), and address the interferon-stimulated response element (ISRE) (Fig. 10.5b). 

Activate cytosolic STAT transcription factors by phosphorylation... 

Receptors Single transmembrane a heUx conserved multi-P strand fold in extracellular domain JAK kinase associated with intracellular domain Signal transduction (1) Direct activation of cytosolic STAT transcription factors ... 

Cloning of the genes identified by this procedure led to recognition of two key signal-transduction proteins a JAK tyrosine kinase and a STAT transcription factor. Subsequent work showed that one (sometimes two) of the four human... 

Receptor-Associated JAK Kinases Activate STAT Transcription Factors Bound to a Cytokine Receptor... 

Interaction of different signaling pathways permits the fine-tuning of cellular activities required to carry out complex developmental and physiological processes. As we have noted previously, both RTKs and cytokine receptors can Initiate signaling via the Ras-MAP kinase pathway, DAG/IP3 pathway, and PT3 kinase pathway (see Table 14-1). In addition, cytokine receptors can act through their associated JAK kinases to direcdy activate STAT transcription factors. 

Levy, D. E., and J. E. Darnell, Jr. 2002. Stats transcriptional control and biological impact. Nature Rev. Mol. Cell Biol. 3 651-62. 

Stimulation of the g and a interferon receptors leads to the activation of Jak kinase family members which phosphorylate a variety of STAT transcription factors. Regulation of interferon-responsive genes is the result of phosphorylation-dependent nuclear translocation and dimerization of STAT transcription factors, which is required to activate their DNA binding and transcriptional regulatory functions. 

---