J Biol Chem 1999,
PMID: 10521450
Craxton, A; Jiang, A; Kurosaki, T; Clark, E A
Activation of Akt by multiple stimuli including B cell antigen receptor (BCR) engagement requires phosphatidylinositol 3-kinase and regulates processes including cell survival, proliferation, and metabolism. BCR cross-linking activates three families of non-receptor protein tyrosine kinases (PTKs) and these are transducers of signaling events including phospholipase C and mitogen-activated protein kinase activation; however, the relative roles of PTKs in BCR-mediated Akt activation are unknown. We examined Akt activation in Lyn-, Syk- and Btk-deficient DT40 cells and B cells from Lyn(-/-) mice. BCR-mediated Akt activation required Syk and was partially dependent upon Btk. Increased BCR-induced Akt phosphorylation was observed in Lyn-deficient DT40 cells and Lyn(-/-) mice compared with wild-type cells suggesting that Lyn may negatively regulate Akt function. BCR-induced tyrosine phosphorylation of the phosphatidylinositol 3-kinase catalytic subunit was abolished in Syk-deficient cells consistent with a receptor-proximal role for Syk in BCR-mediated phosphatidylinositol 3-kinase activation; in contrast, it was maintained in Btk-deficient cells, suggesting Btk functions downstream of phosphatidylinositol 3-kinase. Calcium depletion did not influence BCR-induced Akt phosphorylation/activation, showing that neither Syk nor Btk mediates its effects via changes in calcium levels. Thus, BCR-mediated Akt stimulation is regulated by multiple non-receptor PTK families which regulate Akt both proximal and distal to phosphatidylinositol 3-kinase activation.
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Text Mining Data
Akt → BCR: "
BCR cross linking activates three families of non-receptor protein tyrosine kinases ( PTKs ) and these are transducers of signaling events including phospholipase C and mitogen activated protein kinase activation ; however, the relative roles of PTKs in
BCR mediated
Akt activation are unknown
"
Syk → BCR: "
BCR mediated Akt activation required Syk and was partially dependent upon Btk
"
Syk → Btk: "
BCR mediated Akt activation required Syk and was partially dependent upon Btk
"
Syk → Akt: "
BCR mediated Akt activation required Syk and was partially dependent upon Btk
"
Akt → BCR: "
BCR mediated Akt activation required Syk and was partially dependent upon Btk
"
Akt → Btk: "
BCR mediated Akt activation required Syk and was partially dependent upon Btk
"
Akt → BCR: "
Increased BCR induced Akt phosphorylation was observed in Lyn-deficient DT40 cells and Lyn ( -/- ) mice compared with wild-type cells suggesting that Lyn may negatively regulate Akt function
"
Akt → BCR: "
Thus, BCR mediated Akt stimulation is regulated by multiple non-receptor PTK families which regulate Akt both proximal and distal to phosphatidylinositol 3-kinase activation
"
Manually curated Databases
No curated data.