Role of Phosphorylation in the Control of Clathrin-Mediated Internalization of GPCR

Table 1

Functional role of phosphorylation by Protein Kinase(s) in vitro and in vivo during clathrin-mediated internalization.

Phosphorylation substrates	Kinase	Possible roles	References
Dynamin [Tyr-231 Tyr-597]	Src		[100]
Dynamin	PKC	stimulates GTPase activity	[115]
Dynamin [Thr-780]	Cdk5	Inhibition of Amphiphysin binding	[125]
Angiotensin II type 1 receptor	Src		[143]
β2-AR, prostacyclin receptor	PKA	switch coupling from Gs to Gi	[16, 17]
GPCRs [Ser/Thr] clusters	GRKs	Desensitization, recruitment of arrestins	[26]
AP-2 [𝜇(YxxΦ)]	AAK1	TfR endocytosis	[144]
AP-2 [𝜇(YxxΦ)]	AAK1	α1a AR endocytosis	[145]
AP-2	AAK1	binding to endocytic cargo	[83, 84]
AP-2 [μ]	GAK		[85, 86]
AP-2 [α]	CK2	Inhibition of clathrin binding	[74, 77]
AP-2 [β]	CK2	Inhibition of clathrin binding	[74, 77]
AP-2 [β] [Tyr-737]	c-Src	Inhibition of arrestin binding	[105]
GRK2	PKC	Increase GRK activity	[36, 38]
GRK5	PKC	Decrease GRK activity	[39]
GRK2	c-Src	targets GRK2 for degradation	[40, 41]
β-arrestin 1 [Ser-412]	ERK1,2	Reduce binding to Src and clathrin	[60, 61]
β-arrestin 1 [Ser-412]	GRK5	Block Src activation	[63]
β-arrestin 1 [Tyr-54]	Src	Decrease the interaction with the 𝜇-adaptin	[72]
β-arrestin 2 [Thr-383, Ser-361]	casein kinase II	interaction with unidentified binding partners	[64][65]
Arr2	CaMKII	Unknown	[66]
Clathrin heavy chain	Src	Facilitates membrane binding	[78]
Clathrin Light chain	CK2	Unknown	[75]
Amphiphysin [Thr-350,-387]	CK2	CK2 inhibits interaction with AP-2 and clathrin	[127, 136, 146]
Amphiphysin [Ser-261, 272, 276, 285 and Thr-310]	Cdk5	Inhibits interaction with the beta-subunit of AP-2	[125]
Amphiphysin	MAPK/ERK	Inhibits interaction with AP-2	[135]
Synaptojanin	PKC	Inhibits interaction with binding partners	[123, 127]
Synaptotagmin	CaMKII	Probably inhibitory	[87]
Epsin	Unknown	Inhibits interaction with binding partners	[147]
Eps15	Unknown	Inhibits interaction with AP-2	[147]