Cell survival and proliferation Production of C-1-P bolsters cell survival and
proliferation. It has been shown that C-1-P promotes
DNA synthesis in
fibroblasts. C-1-P also prevents
apoptosis by inhibiting the
caspase-9/
caspase-3 pathway and preventing DNA fragmentation in
macrophages. This is thought to occur via C-1-P interacting with and blocking functionality of
acid sphingomyelinase. This results in diminished ceramide production, which precludes apoptosis. Recently, phosphorylation of ceramide via CERK has been shown to stimulate
myoblast proliferation. It was demonstrated that C-1-P perpetuates the phosphorylation of
glycogen synthase kinase-3 β and
retinoblastoma protein, which contributes to transition from the
G1 phase to
M phase of the
cell cycle. Additionally, production of C-1-P appears to result in increased expression of
Cyclin D. CERK has demonstrated an ability to activate
phosphatidylinositol 3-kinase/
Akt (PI3K/Akt),
ERK1/
2, and
mTOR.
Other roles In addition to cell survival and proliferation, CERK has been implicated in many other processes. CERK is believed to participate in altering the
lipid raft structure via C-1-P production, contributing to
phagosome formation in polymorphonuclear
leukocytes. CERK has also been found to participate in the calcium-dependent degranulation of
mast cells. ==References==