PKC-η mediates glioblastoma cell proliferation through the Akt and mTOR signaling pathways

The protein kinase C-η isoform induces proliferation in glioblastoma cell lines through an ERK/Elk-1 pathway

“…Furthermore, PKC-Z partially increases cell proliferation via Akt, and the mammalian target of rapamycin (mTOR) (Aeder et al, 2004). To date, the signaling pathways by which PKC-Z increases proliferation via MAPK cascades and their transcription factor targets had not been elucidated.…”

“…U-1242-Z cells are U-1242 cells that stably express PKC-Z (Hussaini et al, 2000). U-251-PKC-ZKR cells are U-251 cells that have been virally infected with a PKC-Z dominantnegative, a PKC-Z bearing a lysine-to-arginine mutation in the kinase domain (Aeder et al, 2004). Both lines were determined to be free of mycoplasma on a regular basis, using reagents from Gen-Probe Inc. (San Diego, CA, USA).…”

Phorbol 12-myristate 13-acetate and serum synergize to promote rapamycin-insensitive cell proliferation via protein kinase C-eta

“…Both cell lines were isolated from characterized glioblastoma tumors and these cell lines have been described extensively. Stably infected U-251kr cells have been described previously (Aeder et al, 2004). PKC-Z antisense clones have been described previously (Hussaini et al, 2000).…”

“…We have shown that PKC-Z-expressing cells demonstrate increased rates of PMA-induced cell proliferation and are resistant to radiotherapy (Hussaini et al, 2000(Hussaini et al, , 2002. Activation of PKC isozymes, including PKC-Z, by PMA and other agents promote activation of the PI3K/AKT/mTOR pathway in several cell types, including glioblastomas (Aeder et al, 2004). Although the regulatory functions of many PKC isozymes in controlling cell growth and proliferation have been established in other cells, the function of PKC isozymes in glioblastoma is not well understood.…”

The anti-tumoral drug enzastaurin inhibits natural killer cell cytotoxicity via activation of glycogen synthase kinase-3β

“…PKC activation can trigger signaling through the ras/ERK pathway [47] and/or the PI3K/AKT pathway [7]. PKCα, PKCβ, and PKCε can also directly phosphorylate AKT at Ser 473 , which is essential for AKT activity [48][49][50]. Moreover, both PKC [51,52] and AKT activity [53] can phosphorylate GSK-3β at Ser 9 , indicating an overlap in these signaling pathways.…”