PGF(2alpha) stimulates FP prostanoid receptor mediated crosstalk between Ras/Raf signaling and Tcf transcriptional activation.
Prostaglandin-F(2alpha) (PGF(2alpha)) is a product of the cyclooxygenase pathway and is a local signaling molecule that activates a G-protein coupled prostanoid receptor named FP. FP receptors can stimulate T-cell factor (Tcf) transcriptional activation by stabilization of beta-catenin and can upregulate the expression of mRNA encoding cysteine-rich protein 61 (Cyr61), a secreted extracellular matrix protein that stimulates angiogenesis. We now show in both HEK cells and human microglial cells that the induction of Cyr61 protein expression by the human FP receptor utilizes a novel mechanism involving the activation of Ras and Raf followed by a MEK/ERK independent activation of Tcf signaling. The upregulation of Cyr61 in microglial cells may contribute to glioma tumorigenesis and could be a potential therapeutic target.
Xu
Wei
W
Department of Pharmacology & Toxicology, The University of Arizona, Tucson, 85721-0207, USA.
Chou
Chih-Ling
CL
Israel
Davelene D
DD
Hutchinson
Anthony J
AJ
Regan
John W
JW
D002460:Cell Line; D055515:Cysteine-Rich Protein 61 / Q000235:genetics*; D015237:Dinoprost / Q000494:pharmacology*; D006801:Humans; D017628:Microglia / Q000187:drug effects / Q000378:metabolism; D011982:Receptors, Prostaglandin / Q000819:agonists* / Q000378:metabolism; D051820:TCF Transcription Factors / Q000378:metabolism*; D015533:Transcriptional Activation / Q000187:drug effects*; D048490:raf Kinases / Q000378:metabolism; D018631:ras Proteins / Q000378:metabolism
C501848:CCN1 protein, human; D055515:Cysteine-Rich Protein 61; D011982:Receptors, Prostaglandin; D051820:TCF Transcription Factors; C034671:prostaglandin F2alpha receptor; D015237:Dinoprost; D048490:raf Kinases; D018631:ras Proteins