Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UNIPROT:P14784 (IL-2 receptor)
 3,849 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Members of the recently discovered SOCS/CIS/SSI family have been proposed as regulators of cytokine signaling, and while targets and mechanisms have been suggested for some family members, the precise role of these proteins remains to be defined. To date no SOCS proteins have been specifically implicated in interleukin-2 (IL-2) signaling in T cells. Here we report SOCS-3 expression in response to IL-2 in both T-cell lines and human peripheral blood lymphocytes. SOCS-3 protein was detectable as early as 30 min following IL-2 stimulation, while CIS was seen only at low levels after 2 h. Unlike CIS, SOCS-3 was rapidly tyrosine phosphorylated in response to IL-2. Tyrosine phosphorylation of SOCS-3 was observed upon coexpression with Jak1 and Jak2 but only weakly with Jak3. In these experiments, SOCS-3 associated with Jak1 and inhibited Jak1 phosphorylation, and this inhibition was markedly enhanced by the presence of IL-2 receptor beta chain (IL-2Rbeta). Moreover, following IL-2 stimulation of T cells, SOCS-3 was able to interact with the IL-2 receptor complex, and in particular tyrosine phosphorylated Jak1 and IL-2Rbeta. Additionally, in lymphocytes expressing SOCS-3 but not CIS, IL-2-induced tyrosine phosphorylation of STAT5b was markedly reduced, while there was only a weak effect on IL-3-mediated STAT5b tyrosine phosphorylation. Finally, proliferation induced by both IL-2- and IL-3 was significantly inhibited in the presence of SOCS-3. The findings suggest that when SOCS-3 is rapidly induced by IL-2 in T cells, it acts to inhibit IL-2 responses in a classical negative feedback loop.
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PMID:SOCS-3 is tyrosine phosphorylated in response to interleukin-2 and suppresses STAT5 phosphorylation and lymphocyte proliferation. 1037 48

The activation of Stat5 proteins (Stat5a and Stat5b) is one of the earliest signaling events mediated by IL-2 family cytokines, allowing the rapid delivery of signals from the membrane to the nucleus. Among STAT family proteins, Stat5a and Stat5b are the two most closely related STAT proteins. Together with other transcription factors and co-factors, they regulate the expression of the target genes in a cytokine-specific fashion. In addition to their activation by cytokines, activities of Stat5a and Stat5b, as well as other STAT proteins, are negatively controlled by CIS/SOCS/SSI family proteins. The outcome of Stat5 activation in regulating expression of target genes varies, depending upon the complexity of the promoter region of target genes and the other signaling pathways that are activated by each cytokine as well. Here, we mainly focus on the IL2-/IL-2 receptor system, as it is one of the best-studied systems that depend on Stat5-mediated signals. We will summarize what we have learned about the molecular mechanisms of how Stat5 is activated by IL-2 family cytokines from in vitro biochemical studies as well as the role that is played by Stat5 in each of the cytokine signaling pathways from in vivo gene-targeting analyses. Oncogene (2000).
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PMID:The role of Stat5a and Stat5b in signaling by IL-2 family cytokines. 1085 Oct 55

A number of previous investigations have reported that physical exercise renders immunopotentiating and antitumor therapeutic benefits to the tumor-bearing host. As these effects of physical exercise are mainly mediated through the modulation of hormonal and cytokine repertoire, it remains unclear if male and female tumor-bearing hosts show a gender-dependent differential response to the therapeutic action of physical exercise in tumor growth retardation. In the present investigation tumor growth retardation, following physical exercise was investigated in a gender-specific manner in a murine tumor model of a T-cell lymphoma designated as Dalton's lymphoma (DL). The results of the present investigation show that physical exercise of a tumor-bearing host on a treadmill results in a better retardation of tumor progression along with prolongation of survival time in male compared to female tumor-bearing host. Such gender dimorphism of the therapeutic benefits of physical exercise in tumor-bearing host was found to be associated with a gender-dependent variation in cell survival and induction of apoptosis in tumor cells. Moreover, expression of cell growth regulatory proteins-selectin, Hsp70, p53, CAD, SOCS, and IL-2 receptor-was found to vary in a gender-specific manner following physical exercise. The investigation also indicates the role of cytokines and macrophages in manifestation of gender dimorphism in the response of tumor-bearing mice to physical exercise. Thus, the observations of the present investigation suggest for the first time that the beneficial effects of physical exercise in a tumor-bearing host may be variable depending on the gender of the host.
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PMID:Treadmill exercise-dependent tumor growth retardation in T-cell lymphoma-bearing host displays gender dimorphism. 2037 30