Inflammasome activation controlled by the interplay between post-translational modifications: emerging drug target opportunities

Table 3 Kinases involved in phosphorylation of NLRP3 inflammasome components

Kinase	Activator	Substrate	Phosphorylation site^a	Domain	Molecular or cellular outcome	Refs.
JNK1	LPS	NLRP3	S198 (S194)	Between PYD and NACHT	NLRP3 self-association and activation	[29]
PKD	Golgi dysregulation	NLRP3	S295 (S291)	NACHT	NLRP3 activation	[31]
PKA	Bile acids/PGE2	NLRP3	S295 (S291)	NACHT	Block NLRP3 activation	[27, 30]
EphA2	–	NLRP3	(Y132)	Between PYD and NACHT	Block ASC oligomerization	[32]
IKKα	LPS	ASC	(S16), (S193)	PYD and CARD	Translocation of ASC/negative regulation	[43]
IKKi	LPS	ASC	S58	PYD	Translocation of ASC/positive regulation	[43]
Syk/JNK	LPS	ASC	Y 146 (Y144), (Y187)	CARD	ASC oligomerization	[40, 44]
Pyk2/FAK	MSU^b	ASC	Y146 (Y144)	CARD	ASC oligomerization	[45]
PAK1	LPS	CASP1	S376	Peptidase C14	Caspase-1 auto-cleavage	[49]

^aAmino acid residues shown above refer to human NLRP3, those in brackets refer to mouse NLRP3 residues
^bMSU, monosodium urate

ISSN: 1478-811X