Signal transducers and activators of transcription (STATs) play key roles in growth factor-mediated intracellular signal transduction. In the present study using a constitutively active STAT5 mutant, we show that STAT5 has pleiotropic functions regulating cell proliferation, differentiation and apoptosis in an IL-3-dependent Ba/F3 cell line. The mutant STAT5 possessed constitutive tyrosine phos...

Defects in macrophage colony-stimulating factor (M-CSF) signaling disrupt myeloid cell differentiation in nonobese diabetic (NOD) mice, blocking myeloid maturation into tolerogenic antigen-presenting cells (APCs). In the absence of M-CSF signaling, NOD myeloid cells have abnormally high granulocyte macrophage colony-stimulating factor (GM-CSF) expression, and as a result, persistent activation ...

Aging is associated with significant changes in hematopoiesis, including clonal dominance, anemia, myeloid malignancies, and reduced activation of signal transducer and activator of transcription 5 (Stat5). In previous studies, Stat5 deletion surprisingly amplified FLT3/ITD+ myeloid expansion or Myc-driven lymphoid expansion. Here we show that Stat5 deficiency has a strong impact upon transcrip...

This study was aimed to observe whether expressions of JAK2, STAT1, STAT5 proteins in indomethacin-treated CML cells involved in the proliferation inhibition of CML cells, and elucidate the pharmacological mechanism of indomethacin anti-leukemia. MTT assay and trypan blue dye exclusion test were used to detect the inhibitory effect of indomethacin on CML cells proliferation. JAK2, STAT1, STAT5 ...

The two transcription factors STAT5A and STAT5B are central signaling molecules in leukemias driven by Abelson fusion tyrosine kinases and they fulfill all criteria of drug targets. STAT5A and STAT5B display unique nuclear shuttling mechanisms and they have a key role in resistance of leukemic cells against treatment with tyrosine kinase inhibitors (TKI). Moreover, STAT5A and STAT5B promote sur...

The D816V-mutated variant of Kit triggers multiple signaling pathways and is considered essential for malignant transformation in mast cell (MC) neoplasms. We here describe that constitutive activation of the Stat5-PI3K-Akt-cascade controls neoplastic MC development. Retrovirally transduced active Stat5 (cS5(F)) was found to trigger PI3K and Akt activation, and to transform murine bone marrow p...

IL-2(-/-) mice develop autoimmunity despite having relatively normal numbers of regulatory T cells (Tregs). In contrast, we demonstrate that IL-2(-/-) x IL-15(-/-) and IL-2Rbeta(-/-) mice have a significant decrease in Treg numbers. Ectopic expression of foxp3 in a subset of CD4(+) T cells rescued Treg development and prevented autoimmunity in IL-2Rbeta(-/-) mice, suggesting that IL-2Rbeta-depe...

A burn injury triggers traumatic reactions characteristics of a stress. Here we investigated the early responses of prolactin (PRL), corticosterone (CS), and signal transducer and activator of transcription 5 (STAT5) in male Sprague-Dawley rats after burn injury. PRL and CS levels were determined in blood serum. STAT5 and phospho-STAT5 levels were determined in jejunum total protein extracts. T...

We are interested in understanding the molecular basis of macrophage (Mphi) differentiation and activation by cytokines. Recent reports have suggested that the transcription factor STAT5 may play a role in Mphi differentiation. In the experiments described here, we assessed the expression of STAT5-related molecules in three Mphi cell lines, RAW 264.7, WEHI-3, and WEHI-3D+, which represent diffe...

Erythropoietin has emerged as a potential therapy for the treatment of ischemic tissue injury. In erythroid cells, the JAK2/Y343/STAT5 signaling axis has been shown to be necessary for stress but not steady-state erythropoiesis. The requirement for STAT5 activation in erythropoietin-mediated protection from ischemic injury has not been well-studied. To answer this question, we induced reproduci...