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Target Concepts:
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Query: EC:3.1.4.3 (
phospholipase C
)
18,461
document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)
The production of the second messenger molecules diacylglycerol and inositol 1,4,5-trisphosphate is mediated by activated phosphatidylinositol-specific
phospholipase C
(
PLC
) enzymes. We report the enhancement of the phosphoinositide metabolism pathway in
KMS
-4 and
KMS
-8 cells, both of which are human colorectal carcinoma cell lines derived from familial adenomatous polyposis patients. In these cells, the cellular contents of diacylglycerol and inositol 1,4,5-trisphosphate were constitutively increased and the
PLC
activity in vitro was significantly high, as compared with those in normal colon cells or in other sporadic colorectal carcinoma cells. Northern and Western analyses showed the high expression levels of both
PLC
-gamma 1 and
PLC
-delta 1 in
KMS
-4 and
KMS
-8 cells. Moreover, we detected the enhancement of protein-tyrosine kinase activity and tyrosine phosphorylation of
PLC
-gamma 1 in these
KMS
cells. These results suggest the involvement of activated phosphoinositide signaling pathways in the colorectal tumorigenesis of familial adenomatous polyposis.
...
PMID:Enhanced phosphoinositide metabolism in colorectal carcinoma cells derived from familial adenomatous polyposis patients. 752 18
We reported previously the enhanced phosphoinositide metabolism and constitutive activation of phosphoinositide-specific
phospholipase C
(
PLC
) in two colorectal carcinoma cell lines,
KMS
-4 and
KMS
-8, derived from familial adenomatous polyposis patients. To study the physiological role of enhanced
PLC
activity in these cells, we analyzed the effect of
PLC
inhibitor (PCI) peptides on their growth and cell cycle. N-Myristoylated PCI peptide, myr-PCI(Y), originally developed based on the PCI sequence of
PLC
-gamma 2, inhibited activity of purified
PLC
isoforms in vitro. When myr-PCI(Y) was added to
KMS
-4 and
KMS
-8 cultures, it suppressed the production of inositol trisphosphate, DNA synthesis, and cell growth, all of which were induced by serum in both
KMS
-4 and
KMS
-8 cells. The number of colonies grown in soft agar was also reduced significantly by treating
KMS
-8 cells with myr-PCI(Y) peptide. Flow cytometry analysis with propidium iodide labeling revealed marked decreases in the percentage of
KMS
-8 cells in S phase and increases in G0-G1 by the addition of myr-PCI(Y). On the other hand, myr-PCI(F), in which two of the tyrosine residues in myr-PCI(Y) are replaced by phenylalanine and which does not inhibit phosphatidylinositol 4,5-bisphosphate-hydrolyzing activity in vitro, did not significantly inhibit either inositol trisphosphate production or cell growth. These results indicate that the activation of
PLC
is essential for growth and the transformed properties of these colorectal carcinoma cells.
...
PMID:Growth inhibition by phospholipase C inhibitor peptides of colorectal carcinoma cells derived from familial adenomatous polyposis. 883 58
