Gene interactions and pathways from curated databases and text-mining
Blood 2009, PMID: 19321861

A proliferation-inducing ligand mediates follicular lymphoma B-cell proliferation and cyclin D1 expression through phosphatidylinositol 3-kinase-regulated mammalian target of rapamycin activation.

Gupta, Mamta; Dillon, Stacey R; Ziesmer, Steven C; Feldman, Andrew L; Witzig, Thomas E; Ansell, Stephen M; Cerhan, James R; Novak, Anne J

A proliferation-inducing ligand (APRIL), as well as its receptors transmembrane activator and calcium-modulating cyclophilin ligand (CAML) interactor (TACI) and B-cell maturation antigen (BCMA), has been shown to be important in B-cell biology, and overexpression of APRIL in mice results in development of lymphoma. Limited data are available on APRIL-specific signaling responses, but knockout models suggest that signaling through TACI is critical to B-cell homeostasis. To better understand the mechanism by which APRIL exerts its effects and how it may contribute to lymphomagenesis, we sought to characterize the outcome of APRIL-TACI interactions. In support of murine studies, we find that APRIL induces proliferation of human patient follicular lymphoma (FL) B cells in a TACI-dependent manner. This study also shows that APRIL is expressed within the tumor microenvironment and that, upon engagement with TACI, APRIL mediates activation of the phosphatidylinositol 3-kinase (PI3K) pathway. Activation of PI3K via APRIL results in phosphorylation of Akt and mammalian target of rapamycin (mTOR) and the mTOR-specific substrates p70S6 kinase and 4E-binding protein 1 in a TACI-dependent manner. APRIL-mediated signaling also results in phosphorylation of Rb and up-regulation of cyclin D1. These studies are the first to characterize APRIL-TACI-specific signaling and suggest a role for this ligand-receptor pair in FL B-cell growth.

Diseases/Pathways annotated by Medline MESH: Lymphoma, Follicular
Document information provided by NCBI PubMed

Text Mining Data

cyclin D1 → A proliferation inducing ligand: " A proliferation inducing ligand mediates follicular lymphoma B-cell proliferation and cyclin D1 expression through phosphatidylinositol 3-kinase regulated mammalian target of rapamycin activation "

PI3K ⊣ Akt: " Activation of PI3K via APRIL results in phosphorylation of Akt and mammalian target of rapamycin (mTOR) and the mTOR-specific substrates p70S6 kinase and 4E-binding protein 1 in a TACI dependent manner "

PI3K ⊣ mammalian target of rapamycin (mTOR): " Activation of PI3K via APRIL results in phosphorylation of Akt and mammalian target of rapamycin (mTOR) and the mTOR-specific substrates p70S6 kinase and 4E-binding protein 1 in a TACI dependent manner "

Akt → APRIL: " Activation of PI3K via APRIL results in phosphorylation of Akt and mammalian target of rapamycin (mTOR) and the mTOR-specific substrates p70S6 kinase and 4E-binding protein 1 in a TACI dependent manner "

mTOR-specific → APRIL: " Activation of PI3K via APRIL results in phosphorylation of Akt and mammalian target of rapamycin (mTOR) and the mTOR-specific substrates p70S6 kinase and 4E-binding protein 1 in a TACI dependent manner "

PI3K → APRIL: " Activation of PI3K via APRIL results in phosphorylation of Akt and mammalian target of rapamycin (mTOR) and the mTOR-specific substrates p70S6 kinase and 4E-binding protein 1 in a TACI dependent manner "

cyclin D1 ⊣ APRIL: " APRIL mediated signaling also results in phosphorylation of Rb and up-regulation of cyclin D1 "

Manually curated Databases

No curated data.