Disease relevance of STAT5B

• A selective decrease in STAT5B was seen 8 days after infection with the BZ167 dual-tropic HIV isolate, but not with the Ba-L, M-tropic strain [1].
• Our results suggest a role of STAT5B as a regulator of gene expression in diabetes-associated vascular disease [2].
• In the current study we demonstrate specific activation of STAT5B in epithelial cells representing invasive and metastatic prostate cancer [3].
• Because we also found preferential constitutive STAT5B activation after transformation of cells by a truncated form of the G-CSF-R that produces severe neutropenia (Kostmann syndrome) and favors leukemia in humans, we discuss the potential role of STAT5B in oncogenic transformation of hematopoietic cells [4].

High impact information on STAT5B

• Expression of the protein tyrosine kinase Lck, a key signaling protein in the TCR complex, activated DNA binding of transfected STAT5A and STAT5B to specific STAT inducible elements [5].
• We also examined the T cell precursor activity of progenitors expressing dominant-negative forms of PI-3K or STAT5B [6].
• Diabetic LDL inhibits cell-cycle progression via STAT5B and p21(waf) [2].
• Whereas 94-kD STAT5A was clearly tyrosine phosphorylated and bound to the enhancer element, the gamma response region (GRR), of the Fc gamma RI gene, substantially less tyrosine phosphorylated STAT5B bound to the immobilized GRR element [7].
• These results support our hypothesis that specific activation of STAT5, in particular STAT5B, facilitates the progression of prostate cancer [3].

Biological context of STAT5B

• We report here the cloning of two forms of STAT5, STAT5A and STAT5B, from an IM-9 cDNA library [8].
• Furthermore, we identified two alternative 5' exons in STAT5B genes and thus two alternative promoters [9].
• Two CpG islands, 23.2% CpG for STAT5A and 30.2% for STAT5B, are present at the 5' of both STAT5 genes covering the 5' untranslated regions [9].
• STAT3 and STAT5B are targets of two different signal pathways activated by hematopoietin receptors and control transcription via separate cytokine response elements [10].
• Mutation of tyrosine 595 dramatically prolongs the duration of tyrosyl phosphorylation of the signal transducer and activator of transcription STAT5B in response to GH, while mutation of tyrosine 487 moderately prolongs the duration of STAT5B tyrosyl phosphorylation [11].

Anatomical context of STAT5B

• By the use of specific antibodies, it was determined that only STAT5B, and not STAT5A, was tyrosine phosphorylated in GM-CSF-treated neutrophils [12].
• Freshly isolated monocytes expressed 94-kD STAT5A, 92-kD STAT5B, and an 80-kD STAT5A molecule [7].
• In this work, we aimed to investigate the role of STAT5 in human precursor B cell survival by introducing dominant-negative (DN) forms of STAT5A or STAT5B in the 697 pre-B cell line [13].
• We have reported previously that expression of STAT5B, but not STAT5A, could enhance the transforming potential of v-src and induces cell cycle progression and motility in fibroblasts [3].
• Upon growth hormone treatment, MT-bound STAT5B was rapidly released from microtubules by a dynein-dependent transport to the nucleus [14].

Associations of STAT5B with chemical compounds

• Substitution of these amino acids demonstrated that a glycine residue at position 433 in STAT5B and a glutamic residue at a similar position in STAT5A determined the DNA binding specificity [15].

Physical interactions of STAT5B

• Functional activation is accompanied by STAT5A but little STAT5B nucleoprotein binding to the IFN-gamma STAT5 site, as determined by competition and supershift assays [16].

Regulatory relationships of STAT5B

• Bandshift experiments showed that in an early stage of both differentiation pathways (14 days), the 94 kDa STAT5B protein was activated by both IL-5 (eosinophil lineage) and GM-CSF (neutrophil lineage) [17].

Other interactions of STAT5B

• There were no specificity differences between STAT5A and STAT5B [18].
• STAT5A and STAT5B genes belong to the signal transducer and activators of transcription (STAT) family of transcription factors [9].
• Moreover, STAT5B and STAT3 enhanced gene transcription via separate regulatory elements [10].
• Activation of STAT5B differed from that of the other two in that the box 3 sequence motif in the cytoplasmic domain of gp130 was not required [10].
• In co-transfection assays, prolactin-mediated activation but not src kinase-mediated activation of STAT5B resulted in the induction of a beta-casein promoter-driven reporter construct [19].

Analytical, diagnostic and therapeutic context of STAT5B

• Therefore, activation of STAT5A predominates compared to STAT5B when assayed by direct immunoprecipitation and by evaluation of bound STATs to immobilized GRR [7].
• Antisense oligodeoxynucleotides (ODNs) were applied to block STAT5A and STAT5B at the mRNA level and the RT-PCR method was used to study STAT5 mRNA expression in the cells after incubation with ODNs [20].
• In this study, DNA binding and tyrosine phosphorylation of STAT5A and STAT5B were compared with their subcellular localization determined using indirect immunofluorescence microscopy [19].
• The STAT5B gene was located by radiation hybrid mapping to porcine chromosome 12, within the confidence interval for the fatty acid composition quantitative trait loci, previously identified in an Iberian x Landrace cross [21].

References