Another activation switch for endothelial nitric oxide synthase: why does it have to be so complicated?
Regulation of the endothelial isoform of nitric oxide synthase (eNOS) appears to be much more complex in comparison to that of other NOS isoforms. A recent paper has expanded the regulation of the enzyme to the realm of sphingolipid signaling, specifically implicating that sphingosine 1-phosphate, endothelial differentiation gene (Edg) receptors and Akt kinase induce a signal transduction pathway via phosphorylation of a serine residue in eNOS. Bradykinin, a nonapeptide formed by enzymatic cleavage of a plasma protein precursor, activates eNOS by an independent pathway that does not require serine phosphorylation, suggesting a complex interplay of signals in the control of endothelial formation of nitric oxide.
Marletta
M A
MA
Department of Chemistry, University of California, Berkeley, 94720 1460, USA. marletta@cchem.berkeley.edu
D000818:Animals; D001920:Bradykinin / Q000378:metabolism; D004789:Enzyme Activation; D006801:Humans; D008246:Lysophospholipids; D009569:Nitric Oxide / Q000378:metabolism; D019001:Nitric Oxide Synthase / Q000378:metabolism*; D052250:Nitric Oxide Synthase Type III; D015398:Signal Transduction; D013107:Sphingolipids / Q000378:metabolism*; D013110:Sphingosine / Q000031:analogs & derivatives / Q000378:metabolism
D008246:Lysophospholipids; D013107:Sphingolipids; C060506:sphingosine 1-phosphate; D009569:Nitric Oxide; C496314:NOS3 protein, human; D019001:Nitric Oxide Synthase; D052250:Nitric Oxide Synthase Type III; D013110:Sphingosine; D001920:Bradykinin