Disease relevance of Stat5b

• Transcription factors Stat3 and Stat5b are present in rat liver nuclei late in an acute phase response and bind interleukin-6 response elements [1].

High impact information on Stat5b

• Here we analyze two distinct conserved GH response elements in the rat IGF-I locus that contain paired Stat5b sites [2].
• Each response element binds Stat5b in vivo in a GH-dependent way, as assessed by chromatin immunoprecipitation assays, and consists of one high affinity and one lower affinity Stat5b site, as determined by both qualitative and quantitative protein-DNA binding studies [2].
• In contrast, both DNA binding and transactivation domains of Stat5b are required to mediate PRL induction of the beta-casein promoter [3].
• To understand better the role of Stats in PRL signaling, we cloned rat Stat5b from a PRL-responsive T cell line Nb2 [3].
• Unexpectedly, activated Stat5 was also detected in the nuclei of untreated control rats. cDNA clones representing Stat3 and two isoforms of Stat5b were isolated from a cDNA library prepared with mRNA from rat livers excised at the peak of an experimental acute phase response [1].

Biological context of Stat5b

• To test the role of Stat5b in GH-stimulated IGF-I gene expression, we have delivered modified versions of the protein to pituitary-deficient male rats by quantitative adenovirus-mediated gene transfer [4].
• Characterization of distinct Stat5b binding sites that mediate growth hormone-stimulated IGF-I gene transcription [2].
• Taken together, these results identify an intronic enhancer as a key mediator of GH-induced IGF-I gene transcription working through Stat5b and provide new insight into the molecular architecture of this transcriptional pathway [5].
• Amino acid sequence analysis identified the 86- and 91-kDa species as two forms of the transcription factor Stat3 and the 92-kDa species as the factor Stat5b [1].
• In the present study, we found that EGF induced tyrosine phosphorylation of Stat5b both on Tyr-699, which correlated with specific DNA binding activity, and also on other tyrosine residues [6].

Anatomical context of Stat5b

• We previously showed that Stat5b was activated by EGF in rat hepatocytes in primary monolayer culture [6].
• These effects of AG490 were confirmed in COS cells overexpressing Stat5b [7].
• Moreover, our findings suggest that progenitor and immature Leydig cells are functional targets for GH in the immature rat, suggestive of a role for GH-Stat5b in testicular development [8].
• In this report we provide, to our knowledge, the first evidence of Stat5b protein expression in the testis and characterize the activation of Stat5b by these lactogenic hormones in primary rat progenitor, immature and adult Leydig cells, and mouse MA-10 Leydig tumor cells [8].

Associations of Stat5b with chemical compounds

• However, the combination of AG490 and LY294002 largely prevented PRL-induced Stat5b phosphorylation [7].

Enzymatic interactions of Stat5b

• We now show that signal transducer and activator of transcription-5a (Stat5a) and Stat5b become tyrosine phosphorylated in response to PRL stimulation in rat prostate using prostate organ culture as an experimental model [9].

Regulatory relationships of Stat5b

• Furthermore, these results suggest that the role of Jak2 in activating Stat5b may be through a mechanism other than simply inducing Stat5b phosphorylation [7].

Other interactions of Stat5b

• The Stat5b response to EGF was most pronounced soon (3 h) after plating (early G(1)) and at high cell density (50,000 hepatocytes per cm(2)) [6].
• EGF receptor-mediated, c-Src-dependent, activation of Stat5b is downregulated in mitogenically responsive hepatocytes [6].
• Furthermore, kinase-negative-Jak2, but not AG490, could inhibit Stat5b nuclear translocation and DNA binding [7].
• Furthermore, we show that Stat5a and Stat5b are continuously phosphorylated in rat prostate in vivo, although they are expressed to varying degree in separate lobes of rat prostate [9].
• In freshly isolated hepatocytes, EGF activated Stat1, Stat3, and, particularly, Stat5b [10].

Analytical, diagnostic and therapeutic context of Stat5b

• Expression of Stat5b protein and phosphorylated Stat5b protein were investigated by Western blotting using anti-Stat5b pAb and anti-phospho-Stat5a/b pAb [11].
• The transcription factors signal transducer and activator of transcription (Stat)5a and Stat5b have been implicated in the GH regulation of CYP2C genes in rodent liver [12].

References