Signal Transducer and Activator of Transcription 5b (Stat5b) Serine 193 Is a Novel Cytokine-induced Phospho-regulatory Site That Is Constitutively Activated in Primary Hematopoietic Malignancies

Forskolin-inducible cAMP Pathway Negatively Regulates T-cell Proliferation by Uncoupling the Interleukin-2 Receptor Complex

“…Subsequently, Janus tyrosine kinase 1 (Jak1) and Jak3 are recruited to the ␤ and ␥ c chains, respectively, allowing for autoactivation of both proteins. Activated Jaks then phosphorylate tyrosine residues on the IL-2R␤ chain, creating docking sites for downstream effectors, including signal transducer and activator of transcription 5a/b (Stat5a/b), which associate via their Src homology 2 domains (1) 743 , respectively, dissociate from the receptor, form hetero-or homodimers, and translocate to the nucleus where they mediate transcription of genes important for cell growth and differentiation (2)(3)(4)(5)(6)(7)(8). Conversely, this signaling pathway is negatively regulated by three families of proteins, suppressor of cytokine signaling, protein tyrosine phosphatases, and protein inhibitors of activated Stats (PIAS), which target different levels within the Jak/Stat signaling cascade (reviewed in Ref.…”

Phytocomponent 4-hydroxy-3-methoxycinnamaldehyde ablates T-cell activation by targeting protein kinase C-θ and its downstream pathways

“…High expression of PKCθ and PKCα in T cells and their crucial roles in T-cell activation have established that PKCθ and PKCα are attractive immunomodulator for therapy of autoimmune diseases. In activated T cells, tyrosine phosphorylation of PKCθ regulates the translocation and activation of PKCθ signals that lead to the boosted transcriptional activity of NF-κB, and AP-1, which in turn, is essential for induction of the IL2 and other cytokine genes in activated T cells [35][36][37]. Recently, PKCα −/− peripheral CD3 + T cells were reported to have a strong defect in IL-2 production [38].…”

Interleukin-2 Receptor β Thr-450 Phosphorylation Is a Positive Regulator for Receptor Complex Stability and Activation of Signaling Molecules

“…The pcDNA3.1 human JAK3 and STAT5B cDNAs (OriGene) were obtained as described previously (31,34). Mutant forms of IL-2R␤ were prepared using the QuikChange site-directed mutagenesis kit (Stratagene) according to the instructions of the manufacturer.…”