Table 1

Effects of kinases on P-gp and BCRP

TransporterKinase involvedEffect on transporter
(Phosphorylation sites)
References
P-gp (ABCB1)PKCAssociates with P-gp, activator increases transport activity (Ser661 and Ser671, one or more of Ser 667, 675 and 683)Chamber et al., 1992, 1993; Yang et al., 1996
Pim-1Associates with P-gp and maintains glycosylated transporter on cell surface (possibly Ser683)Xie et al., 2010
MEK-ERK-RSKInhibitor promotes degradation of P-gpKatayama et al., 2007
Src in different cellular systemsFlk-1 & SrcReduces transporter function through phosphorylation of caveolin-1Hawkins et al., 2010
Src & Rack1Src increases caveolin-1 phosphorylation and reduces its association with P-gp, increases transporter functionFan et al., 2019
Abl & SrcIncreases caveolin-1 phosphorylation and internalization, reduces P-gp membrane level and transport functionHoshi et al., 2020
KGFR
(MAPK-dependent)
Short-term KGF2 treatment: increases cell surface protein level and activity
Long-term KGF2 treatment: increases mRNA and protein level
Saksena et al., 2013
EGFRIncreases P-gp phosphorylation and activity through PLC
Cetuximab increases membrane expression and activity through PI3K/Akt and MAPK/ERK pathways
Yang et al., 1997;
Caetano-Pino et al., 2017
BCRP (ABCG2)Pim-1LPhosphorylates BCRP, inhibitors affect total and/or cell surface level of the transporter (Thr362)Xie et al., 2008; Natarajan et al., 2013; Darby et al., 2015
EGFRIncreases cell surface protein level through PI3K/ Akt pathway
Cetuximab suppresses membrane expression and activity through PI3K/Akt and MAPK/ERK pathways
Crawford et al., 2018
Caetano-Pino et al., 2017
JAK3Phosphorylates and promotes membrane localization of the transporter (possibly Tyr123, Tyr273, Tyr336)Mishra et al., 2019