Phospholipase Cgamma1 stimulates transcriptional activation of the matrix metalloproteinase-3 gene via the protein kinase C/Raf/ERK cascade.
The phospholipid hydrolase phospholipase Cgamma1 (PLCgamma1) plays a major role in regulation of cell proliferation, development, and cell motility. Overexpression of PLCgamma1 is associated with tumor development, and it is overexpressed in some tumors. Matrix metalloproteinase-3 (MMP-3) is a protein involved in tumor invasion and metastasis. Here, we demonstrate that overexpression of PLCgamma1 stimulates MMP-3 expression at the transcriptional level via the PKC-mediated Raf/MEK1/ERK signaling cascade. We propose that modulation of PLCgamma1 activity might be of value in controlling the activity of MMPs, which are important regulators of invasion and metastasis in malignant tumors.
Shin
Soon Young
SY
Institute of Natural Science and Technology, Hanyang University, Ansan 426-791, South Korea.
Choi
Ha Young
HY
Ahn
Bong-Hyun
BH
Min
Do Sik
do S
Son
Sang Wook
SW
Lee
Young Han
YH
D000818:Animals; D002465:Cell Movement / Q000502:physiology; D002478:Cells, Cultured; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism*; D015971:Gene Expression Regulation, Enzymologic; D019278:Matrix Metalloproteinase 3 / Q000096:biosynthesis / Q000235:genetics*; D051379:Mice; D041681:NIH 3T3 Cells; D051966:Phospholipase C gamma / Q000502:physiology*; D011401:Promoter Regions, Genetic / Q000187:drug effects; D011493:Protein Kinase C / Q000378:metabolism*; D051381:Rats; D015398:Signal Transduction / Q000502:physiology*; D014945:Wound Healing / Q000502:physiology; D048490:raf Kinases / Q000378:metabolism*
D048490:raf Kinases; D011493:Protein Kinase C; D048049:Extracellular Signal-Regulated MAP Kinases; D051966:Phospholipase C gamma; D019278:Matrix Metalloproteinase 3