The role of Stat5a and Stat5b in signaling by IL-2 family cytokines

Lin, Jian-Xin

doi:10.1038/sj.onc.1203523

Cited by 320 publications

(274 citation statements)

References 159 publications

Supporting

Mentioning

267

Contrasting

Order By: Relevance

“…Stat5 is one of the key downstream molecules mediating IL-2 signaling [17]. To test whether the IL-2's role in Th2 differentiation is through Stat5 activation, Stat5a-deficient CD4 T cells were used for Th2 priming.…”

Section: Il-2 and Stat5 In Th2 Differentiationmentioning

confidence: 99%

“…A constitutively active form of Stat5a (STAT5A1*6) [18] was introduced by retroviral infection into CD4 T cells during Th2 priming; it was found that expression of STAT5A1*6 fully rescued the IL-4 producing capacity of the cells primed under Th2 conditions in the absence of IL-2, suggesting that Stat5 activation is sufficient to transduce IL-2 signaling for Th2 priming [12]. Many other cytokines including IL-4, IL-7, IL-9 and IL-15 also activate Stat5 [17]; however, the degree of Stat5 tyrosine phosphorylation in these CD4 T cells was greatest in response to IL-2 [12]. In addition, in Stat5a-deficient cells, IL-2 can still activate Stat5b.…”

Section: Il-2 and Stat5 In Th2 Differentiationmentioning

confidence: 99%

See 1 more Smart Citation

GATA-3 promotes Th2 responses through three different mechanisms: induction of Th2 cytokine production, selective growth of Th2 cells and inhibition of Th1 cell-specific factors

et al. 2006

View full text Add to dashboard Cite

Naïve CD4 T cells can differentiate into at least two different types of T helpers, Th1 and Th2 cells. Th2 cells, capable of producing IL-4, IL-5 and IL-13, are involved in humoral immunity against extracellular pathogens and in the induction of asthma and other allergic diseases. In this review, we summarize recent reports regarding the transcription factors involved in Th2 differentiation and cell expansion, including Stat5, Gfi-1 and GATA-3. Stat5 activation is necessary and sufficient for IL-2-mediated function in Th2 differentiation. Enhanced Stat5 signaling induces Th2 differentiation independent of IL-4 signaling; although it does not up-regulate GATA-3 expression, it does require the presence of GATA-3 for its action. Gfi-1, induced by IL-4, promotes the expansion of GATA-3-expressing cells. Analysis of conditional Gata3 knockout mice confirmed the critical role of GATA-3 in Th2 cell differentiation (both IL-4 dependent and IL-4 independent) and in Th2 cell proliferation and also showed the importance of basal GATA-3 expression in inhibiting Th1 differentiation.

show abstract

Section: Il-2 and Stat5 In Th2 Differentiationmentioning

confidence: 99%

Section: Il-2 and Stat5 In Th2 Differentiationmentioning

confidence: 99%

GATA-3 promotes Th2 responses through three different mechanisms: induction of Th2 cytokine production, selective growth of Th2 cells and inhibition of Th1 cell-specific factors

et al. 2006

View full text Add to dashboard Cite

show abstract

“…Capture of IL-2 and binding to/formation of the high-affinity trimer results in activation of JAKs and downstream activation of MAP and STAT5 signaling pathways ( Fig. 2) (Lin and Leonard 2000;Gaffen 2001). …”

Section: Ligand and Receptor Biologymentioning

confidence: 99%

Small-Molecule Inhibitors of IL-2/IL-2R: Lessons Learned and Applied

Wilson

Arkin

2010

Current Topics in Microbiology and Immunology

View full text Add to dashboard Cite

“…During cytokine or growth factor stimulation, STATs are tyrosine phosphorylated, dimerise, and translocate into the nucleus to regulate target gene expression (Darnell, 1997). The activation duration of STATs under physiological conditions is usually temporary and is tightly regulated by a number of cellular mechanisms, such as tyrosine dephosphorylation, ubiquitin/ proteosome-mediated degradation, negative feedback loop mediated by CIS/SOCS/JAB/SSI family of proteins, or inhibition of STAT DNA-binding activity through association with protein inhibitor of activated STAT (PIAS) proteins (Lin and Leonard, 2000). However, constitutively activated STATs, especially STAT1, STAT3 and STAT5, have been found in a variety of human tumours and cancer cell lines, including blood malignancies and solid tumours (Turkson and Jove, 2000).…”

mentioning

confidence: 99%

Constitutive activation of STAT3 and STAT5 is present in the majority of nasopharyngeal carcinoma and correlates with better prognosis

et al. 2003

View full text Add to dashboard Cite

Constitutively activated signal transducers and activators of transcription (STAT) factors, in particular STAT1, STAT3 and STAT5, have been demonstrated in a variety of human tumours and cancer cell lines. However, data on the expression of these STATs in nasopharyngeal carcinoma (NPC) are limited. In this study, the expression patterns of STAT1, STAT3 and STAT5 were immunohistochemically examined on the archival specimens from 61 patients with NPC. Staining results of each STATs were then correlated with the clinical parameters and prognosis of these patients. The results showed that constitutive activation of STAT3 and STAT5 was detected in the majority, 70.5 and 62.3%, respectively, of the 61 tumour specimens. Furthermore, coexpression of activated STAT3 and STAT5 was found in 54.1% of the specimens. In contrast, constitutive activated STAT1 could only be detected in 8 (13.1%) cases. Surprisingly, following radiotherapy, patients with constitutive STAT5 activation, or activation of both STAT3 and STAT5, had better disease-free survival and overall survival than those without activated STAT5. To our knowledge, this is the first report providing the overall expression patterns and prognostic significance of specific STATs in NPC.

show abstract

The role of Stat5a and Stat5b in signaling by IL-2 family cytokines

Cited by 320 publications

References 159 publications

GATA-3 promotes Th2 responses through three different mechanisms: induction of Th2 cytokine production, selective growth of Th2 cells and inhibition of Th1 cell-specific factors

GATA-3 promotes Th2 responses through three different mechanisms: induction of Th2 cytokine production, selective growth of Th2 cells and inhibition of Th1 cell-specific factors

Small-Molecule Inhibitors of IL-2/IL-2R: Lessons Learned and Applied

Constitutive activation of STAT3 and STAT5 is present in the majority of nasopharyngeal carcinoma and correlates with better prognosis

Contact Info

Product

Resources

About