Endothelial cell interactions enzyme activity

Similar to nNOS, Ca2+-activated calmodulin is important for the regulation of eNOS activity. However, several other proteins interact with eNOS and regulate its activity. Heat shock protein 90 (hsp90) is found associated with eNOS and probably acts as an allosteric modulator that activates the enzyme. Caveolin-1 binds eNOS and directs it to caveolae. Caveolin-1 is viewed as an inhibitor of eNOS activity, which is being replaced by CaM upon activation of endothelial cells [2]. 

Garcia-Cardena reported in 1996 that the tyrosine phosphorylation of eNOS in bovine aortic endothelial cells (BAEC) resulted in a decrease in enzyme activity whilst immunoprecipitation of caveolin-1, the predominant isoform in endothelial cells, resulted in co-immunoprecipitation of tyrosine phosphorylated eNOS [17]. Michel et al. (1997) further reported that eNOS, also in BAEC, was co-immunoprecipitaed by caveolin-1 antibodies whilst in rat myocytes eNOS was associated with caveolin-3, the cardiac muscle specific type, confirming that eNOS interaction with caveolin is not tissue specific [18]. Immunofluoresence studies in our group have shown that eNOS associates with caveolin-1 in human umbilical vein endothelial cells (HUVEC), and this interaction is abolished by bradykinin (Wyatt, Pedley Mann, 2001 unpublished data) (Figure 3). 

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