Phosphatases in toll-like receptors signaling: the unfairly-forgotten

Table 2 Protein phosphatases involved in TLRs signaling

	Targets	Residues	Upstream	Effects	Cell types	References
PTPN4	TRAM	Y167	TLR4		Peritoneal and RAW264.7 macrophages	[82]
PTP-PEST	IKK-β	Y188 Y199	TLR3, TLR4, TLR9	↓	RAW264.7 macrophages	[104]
DUSPs (1, 4, 16)	ERK1/2	T202 Y204	TLR2, TLR4, TLR9	↓	RAW264.7 macrophages and BMMs	[105,106,107,108,109,110]
	JNK1/2	T183/Y185
	P38	T180/Y182
PP1	IKK-α	S180	TLR4	↓	RAW264.7 macrophages	[111]
	IKK-β	S181
	TAK1	S412	TLR3, TLR4, TLR9			[112]
	IRF3	S385 S396	TLR3, TLR4		RAW264.7 macrophages and BMMs	[113]
	IRF7	S471 S472 S477 S479	TLR3		RAW264.7, U-937	[114]
PP2A	c-Jun	T239	TLR4	↑	RAW264.7 macrophages	[115, 116]
	IRF3	S396	TLR3, TLR4	↓		[117]
PP4	TBK1	S172			RAW264.7, BMDCs and peritoneal macrophages	[118]
WIP1	p65	S536	TLR4		Splenocytes and astrocytes	[119, 120]

BMMs, Bone Marrow-derived Macrophages; DUSPs, Dual-Specificity Phosphatases; ERK, Extracellular signal-Regulated Kinases; IKK-α, IκB Kinase-α; IKK-β, IκB Kinase-β; IRF3, Interferon Regulatory Factor 3; IRF7, Interferon Regulatory Factor 7; JNK, c-Jun N-terminal Kinase; MEFs, Mouse Embryonic Fibroblasts; PP1, Protein Phosphatase 1; PP2A, Protein Phosphatase 2 A; PP4, Protein Phosphatase 4; PTPN4, Protein Tyrosine Phosphatase, Non-receptor type 4; PTP-PEST, Protein Tyrosine Phosphatase-PEST; RAW264.7, mouse macrophage cell line; S, Serine; T, Threonine; TAK1, Transforming growth factor-β-Activated Kinase 1; TBK1, TANK-Binding Kinase 1; TLR, Toll-Like Receptor; TRAM, TRIF-Related Adaptor Molecule; U-937, human macrophage cell line; WIP1, Wild-type p53-Induced Phosphatase 1; Y, Tyrosine

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