Читать книгу Drug Transporters - Группа авторов - Страница 94

Short‐term regulation of transporter activity can be accomplished through numerous cellular signaling pathways involving phosphorylation and dephosphorylation. In HEK293 cells expressing hMATE1 or hMATE2‐K, pharmacological inhibition of casein kinase II can stimulate transporter activity [74]. Blockade of another kinase, p56^lck tyrosine kinase, also greatly enhanced hMATE2‐K activity; however, this upregulation of function was absent under more acidic conditions. Conversely, a modest reduction in hMATE1 activity could be observed with inhibition of p56^lck tyrosine kinase, as well as calcium/calmodulin [74]. Activation of protein kinases A and C attenuated hMATE2‐K function but had no effect on hMATE1. Clearly, the short‐term regulation of hMATE1 and hMATE2‐K activity is dynamic with multiple phosphorylation events able to turn on/off activity within minutes.