Interferon‐α activates signal transducers and activators of transcription 5 and 6 in Daudi cells

Abstract

In most cells studied so far, interferon-A (IFN-A) activates signal transducer and activator of transcription (Stat1), Stat2 and Stat3, whereas interferon-γ (IFN-γ) induces Stat1 only. In general, each of the several dozens of cytokines, growth factors and hormones that signal through the Janus kinases-signal transducers and activators of transcription (Jak-STAT) pathway activates a distinct subset of STATs, and this selectivity is thought to be essential for the specificity of the cellular responses toward these ligands. Here, we have studied the pattern of STAT activation in the human lymphoblastoid cell line Daudi in response to IFN-A. In addition to Stat1, Stat2 and Stat3 activation, IFN-A was found to directly induce activation of Stat5 and Stat6. Cell-type-specific activation of additional STATs could be responsible for cell-type-specific responses to IFN-A.Keywords : interferon; signal transducers and activators of transcription ; cytokine receptor; signal transduction; transcription factor. Cytokines, interleukins, polypeptide growth factors and hor-The activated Jaks phosphorylate one or more tyrosine residues on receptor chains. The phosphorylated tyrosine residues, tomones bind to receptors on the surface of target cells and elicit diverse and specific responses. The signals received at the recep-gether with the surrounding amino acids, provide the docking sites for the STATs which bind these residues by means of their tors are transmitted by intracellular signal-transduction pathways and result in transcriptional activation of target genes. To evoke SH2 domains. This interaction is specific and provides a bases for differential STAT activation by different polypeptide ligands diverse cellular responses, different ligands have to activate dif- [15,16]. Once recruited to the receptors, STATs become phosferent subsets of genes. This can be achieved through the spephorylated on a single tyrosine residue in the C-terminus and cific activation of particular transcription factors. The signal form homodimers and heterodimers [17]. The specificity of inditransducers and activators of transcription (STATs) are a family vidual STAT SH2 domains for phosphotyrosine motives of the of transcription factors that are activated by many diverse polypartner STAT again determines which homodimer and heteropeptide ligands [1]. For these ligands, STATs serve an important dimers are formed [16]. STAT dimers translocate into the nufunction by contributing to specific gene activation. STATs have cleus, bind to response elements in the promotors of target several properties which suite them as specific signal transducgenes, and activate transcription.

Dysregulated Sonic hedgehog signaling and medulloblastoma consequent to IFN-α–stimulated STAT2-independent production of IFN-γ in the brain

“…These include the STAT transcriptional factors STAT3 (21,22) and STAT5 (23). Whether the activation of alternative signaling pathways involving activated STAT3 and STAT5 in response to IFN requires STAT2 is unclear.…”

Direct Effects of Type I Interferons on Cells of the Immune System

“…10-13). STAT4 and STAT6 can also be activated by IFN-a; however, this activation seems to be restricted to certain cell types, such as endothelial or lymphoid cells (14)(15)(16)(17). Following 10,11,18,19), which translocate to the nucleus and bind other regulatory sequences known as IFN-g-activated sites (GAS).…”

Cell-type and Donor-specific Transcriptional Responses to Interferon-α

“…STAT3 is activated in a variety of cell types (30) and IFN-␣2a directly activates (in addition to STATs 1, -2, and -3) STAT5 and -6 in Daudi cells (31), STAT4 in T cells and natural killer cells (32), and STAT5 in undifferentiated promonocytic U937 cells (33). Moreover, JAK/STAT signaling is essential but not sufficient for full IFN responses.…”