Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P00750 (PLA)
 16,800 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Sphingosine 1-phosphate (S1P) is a bioactive lipid, stored and released from activated platelets, macrophages, and other mammalian cells. We previously reported that S1P induces esophageal smooth muscle contraction in freshly isolated intact cells. Here, we measured S1P-induced ERK1/2 activation and upstream signaling in cultured feline esophageal smooth muscle cells. Activation of ERK1/2 by S1P peaked at 5 min, was sustained up to 30 min, and was blocked by PTX. In contrast, S1P did not activate p38 MAPK or JNK. PTX inhibited S1P-induced ERK1/2 activation. We then used phospholipase inhibitors, DEDA for PLA(2), U73122 for PLC, and rhoCMB for PLD, to determine that ERK1/2 activation was downstream of PLC activation. The PKC inhibitors, GF109203X and chelerythrine, also suppressed ERK1/2 activation. Whereas the PTK inhibitor, genistein, partially inhibited ERK1/2 activation, the EGFR tyrosine kinase inhibitor, tyrphostin 51, had no effect. Taken together, S1P-induced ERK1/2 activation in cultured ESMCs requires a PTX-sensitive G protein, stimulation of the PLC pathway, and subsequent activation of the PKC and PTK pathways.
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PMID:Signaling mechanisms of sphingosine 1-phosphate-induced ERK1/2 activation in cultured feline esophageal smooth muscle cells. 1902 40

We investigated the ability of the sPLA(2), known as MT-III, isolated from the viperid snake Bothrops asper, to induce LB formation in macrophages and the major cellular signaling pathways involved in this process. The effects of MT-III on ADRP localization and expression and macrophage ultrastructure were assessed. Our results showed that this sPLA(2) induced a marked increase in LB numbers in macrophages, induced the recruitment of ADRP in macrophages, and up-regulated ADRP expression. Ultrastructural analysis showed the presence of weakly and strongly osmiophilic LBs in sPLA(2)-stimulated cells. Enlargement of the ER and Golgi cisterns was also observed. Pretreatment of cells with H7 or staurosporine (PKC inhibitors), LY294002 or wortmannin (PI3K inhibitors), SB202190 or PD98059 (p38(MAPK) and ERK1/2 inhibitors, respectively), or Pyr-2 or Bel (cPLA(2) and iPLA(2) inhibitors, respectively) significantly reduced sPLA(2)-induced LB formation. Herbimycin (a PTK inhibitor) and indomethacin or etoricoxib (COX inhibitors) failed to alter sPLA(2)-induced effects. In conclusion, our results show for the first time the ability of a venom sPLA(2) to induce the formation of LBs and the expression of ADRP in macrophages. Venom PLA(2)-induced LB formation is dependent on PKC, PI3K, p38(MAPK), ERK1/2, cPLA(2), and iPLA(2) signaling pathways but not on PTK, COX-1, or COX-2 pathways. Activation of the ER and Golgi complex may play an important role in the formation of LBs induced by this sPLA(2) in macrophages.
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PMID:A group IIA-secreted phospholipase A2 from snake venom induces lipid body formation in macrophages: the roles of intracellular phospholipases A2 and distinct signaling pathways. 2147 70