Interleukin-11 (IL-11) is a multifunctional cytokine belonging to the IL-6 family, known for its diverse roles in various physiological processes. One of its primary functions is to regulate hematopoiesis, particularly in the development and differentiation of megakaryocytes and platelets. Additionally, IL-11 plays a crucial role in the maintenance of bone homeostasis by promoting osteoclast formation and bone resorption. Moreover, it has been implicated in the modulation of immune responses, wound healing, and gastrointestinal mucosal protection. The activation of IL-11 signaling pathways initiates downstream cascades that mediate its diverse biological effects.
Activation of IL-11 primarily occurs through the binding of IL-11 to its specific cell surface receptor, IL-11Rα, leading to the formation of a functional IL-11/IL-11Rα complex. This complex subsequently recruits and activates the shared signal transducer, gp130, which is a common component of the IL-6 cytokine family receptors. Upon activation, gp130 initiates intracellular signaling cascades, including the Janus kinase (JAK)/signal transducer and activator of transcription (STAT) pathway, the mitogen-activated protein kinase (MAPK) pathway, and the phosphoinositide 3-kinase (PI3K)/protein kinase B (Akt) pathway. These signaling pathways regulate gene expression, cell proliferation, survival, and differentiation, thereby mediating the biological responses to IL-11 stimulation. Furthermore, IL-11 signaling can crosstalk with other signaling pathways, such as the transforming growth factor-beta (TGF-β) pathway, to modulate cellular functions in a context-dependent manner. Overall, understanding the mechanisms of IL-11 activation provides insights into its diverse physiological roles and applications in various pathological conditions.
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