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In vivo , using KO mice for either GRK3 or 5, morphine rather promotes MOR phosphorylation at S375 by both kinases while only GRK3 was required for fentanyl-induced MOR phosphorylation (Glck et al., The tyrosine kinase Src was also shown to phosphorylate MOR at Y336, located in the NPXXY motif, after sustained morphine treatment followed by naloxone (Zhang et al., 2009)