Table 2.

Mutations of T‐cell receptor (TCR) ‐CD3 binding proteins with their effects on TCR signalling

TCR–CD3 binding proteins	Mutations	Effects on TCR signalling	References
Lck	R154K (SH2 mutant)	Inhibits Lck association with ZAP‐70 and CD3ζ	38
	Y192F	Inhibits Lck association with TSAd, Itk, Pyk2 and SHP‐1 and enhances tyrosine‐phosphorylated proteins	87
	Y394F	Closed conformation with decreased kinase activity	35, 88
	Y505F	Open conformation with increased enzymatic activity	35, 88
	Y505F, K273R	Open conformation but lacking kinase activity	35
ZAP70	Y315F	Inhibition of Vav–ZAP‐70 interaction and reduction of tyrosine phosphorylation	89
	Y319F	Impairment of Ca2+ mobilization, Ras activation and activation of phospholipase Cγ1	54
	W131A	Increases kinase activity of ZAP‐70	90
	Y315, 319A	Open conformation with increased kinase activity of ZAP‐70	51
	Y315, 319F	Closed conformation with ZAP‐70 kinase inactive	51
	D461N	Inactivates the kinase domain known as ‘kinase dead’	50
	Y493F	Inactivates ZAP‐70 catalytic activity	91
Nck	Nck1(W38K) (SH3.1 mutant)	Impairs the binding of Nck1 to CD3ε and decreases ERK activation	65
	Nck1(W143K) (SH3.2 mutant)	Impairs the binding of Nck1 to Cbl	92
	Nck1(W229K) (SH3.3 mutant)	Impairs the expression of CD69 expression and ERK phosphorylation	63
	Nck1(R308K) (SH2 mutant)	Impairs the binding of Nck1 to CD3ε Abrogates the binding of Nck1 to ADAP	65, 93
WASP	WASPΔC (deletion of amino acids 444–502 at C terminus)	Inhibits actin polymerization but enhances the activation of NFAT transcription factor and ERK phosphorylation in human T cells	94
	L46P (WH1 mutant)	Impairs the chemotactic migration of human T cells and actin cytoskeleton reorganization	95
	A47D (WH1 mutant)	Impairs the chemotactic migration of human T cells and actin cytoskeleton reorganization	95
Numb	ΔNumb (condition deletion of Numb)	Normal CD3ζ phosphorylation in murine T cells	96