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April Mediated Signaling

A proliferation-inducing ligand (APRIL), also known as TNF and ApoL related leukocyte expressed ligand 2 (TALL2), is a recently identified TNF ligand family member implicated in immune regulation. APRIL is a type II membrane protein with a predicted cytoplasmic domain, a hydrophobic transmembrane region and an extracellular domain of 201 amino acids. APRIL shows a unique maturation pathway among the TNF ligand family members as it is not detectable as a membrane anchored protein at the cell surface, but is processed in the golgi apparatus prior to its secretion. APRIL acts solely as a secreted factor.Two members of the TNF receptor family, the transmembrane activator and calcium modulator cyclophilin ligand interactor (TACI) and B-cell maturation antigen (BCMA), have been identified as receptors that can bind APRIL...

April Mediated Signaling

Pathway Summary

A proliferation-inducing ligand (APRIL), also known as TNF and ApoL related leukocyte expressed ligand 2 (TALL2), is a recently identified TNF ligand family member implicated in immune regulation. APRIL is a type II membrane protein with a predicted cytoplasmic domain, a hydrophobic transmembrane region and an extracellular domain of 201 amino acids. APRIL shows a unique maturation pathway among the TNF ligand family members as it is not detectable as a membrane anchored protein at the cell surface, but is processed in the golgi apparatus prior to its secretion. APRIL acts solely as a secreted factor.Two members of the TNF receptor family, the transmembrane activator and calcium modulator cyclophilin ligand interactor (TACI) and B-cell maturation antigen (BCMA), have been identified as receptors that can bind APRIL. APRIL promotes B-cell proliferation by binding to the BCMA and TACI receptors, which are expressed on resting and activated B-cells. In addition, TACI has been found on a subset of activated T cells.Engagement of BCMA activates JNK, p38 MAPK and the transcription factors NF-κB and Elk1 via TRAF1, 2 and 3, whereas cross-linking of TACI activates the transcription factors NF-κB and NFAT. TACI intracellular domain interacts with TRAF 2, 5, and 6 and transduces signals necessary for B-Cell proliferation and survival. TRAFs recruit IKK-activating kinases such as NIK, MEKK1 and TAK1 to phosphorylate IKK, which leads to NF-κB activation. A family of inhibitory proteins, IκBs, binds to NF-κB and controls the activity of NF-κB. Exposure of cells to extracellular stimuli that perturb redox balance results in rapid phosphorylation, ubiquitination, and proteolytic degradation of IκBs. This process frees NF-κB from the NF-κB/IκB complex and enables NF-κB to translocate to the nucleus where it regulates gene transcription.APRIL is predominantly expressed in malignant tumors and promotes growth in several malignant tumor cell lines in vitro and in vivo.

April Mediated Signaling Genes list

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