The identification of DL-threo dihydrosphingosine and sphingosine as novel inhibitors of extracellular signal-regulated kinase signalling in airway smooth muscle.
We present entirely novel evidence that DL-threo dihydrosphingosine and sphingosine are inhibitors of the extracellular signal-regulated kinase (ERK) signalling cassette in mammalian cells. We show that DL-threo dihydrosphingosine is effective against both growth factor- and G-protein-dependent activation of ERK. We conclude that DL-threo dihydrosphingosine may represent an important pharmacological cell-permeable agent that may be usefully employed to block smooth muscle cell proliferation.
Tolan
D
D
Department of Physiology and Pharmacology, University of Strathclyde, Glasgow.
Conway
A M
AM
Steele
L
L
Pyne
S
S
Pyne
N J
NJ
D000818:Animals; D001920:Bradykinin / Q000494:pharmacology; D017871:Calcium-Calmodulin-Dependent Protein Kinases / Q000037:antagonists & inhibitors*; D002478:Cells, Cultured; D004789:Enzyme Activation / Q000187:drug effects; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D006168:Guinea Pigs; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3; D020928:Mitogen-Activated Protein Kinases; D009130:Muscle, Smooth / Q000187:drug effects* / Q000201:enzymology* / Q000502:physiology; D010982:Platelet-Derived Growth Factor / Q000494:pharmacology; D015398:Signal Transduction / Q000187:drug effects* / Q000502:physiology*; D013110:Sphingosine / Q000031:analogs & derivatives* / Q000494:pharmacology*; D013268:Stimulation, Chemical; D014132:Trachea / Q000187:drug effects* / Q000201:enzymology* / Q000502:physiology
D004791:Enzyme Inhibitors; D010982:Platelet-Derived Growth Factor; D017871:Calcium-Calmodulin-Dependent Protein Kinases; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3; D020928:Mitogen-Activated Protein Kinases; D013110:Sphingosine; C005682:safingol; D001920:Bradykinin