Table 1 SFKs involved in regulating... | American Society of Hematology

Table 1

SFKs involved in regulating platelet activation

Subfamily	Src kinase	Species	Interacting proteins	Substrates	Receptor signaling regulated by SFKs	Phenotypes of knockout mouse models
SrcA	Src	Human²⁶	β3,³¹ GPIbα,⁷¹ SHIP-1⁴⁴	β3,⁹⁵ FcγRIIA,⁴³ SHIP-1⁴⁴	αIIbβ3,^25,31,44 α2β1,⁹⁶ α6β1⁹⁷	Reduced αIlbβ3-mediated signaling and functional responses^21,31
	Src	Mouse^21,31	β3,³¹ GPIbα,⁷¹ SHIP-1⁴⁴	β3,⁹⁵ FcγRIIA,⁴³ SHIP-1⁴⁴	GPIb-IX-V,⁷¹ PAR-1, PAR-4,^6,83 TP,⁹⁸ α_2A⁹⁹
	Yes	Human^16,19	β3²⁵	Unknown	αIIbβ3,¹⁰⁰ PAR-1, PAR-4¹⁰¹
	Fyn	Human¹⁸	GPVI,⁵⁰ β3,⁶² PECAM-1⁶⁰	FcR γ-chain,^50,51 PKCδ⁷³	αIIbβ3,⁶² GPVI-FcR γ-chain,^50,51 GPIb-IX-V,⁷⁵ PAR-1, PAR-4,^7,12 P2Y₁₂⁷	Reduced unknown αIIbβ3-mediated signaling and functional responses^21,62
		Mouse⁵¹				Reduced GPVI-FcR γ-chain–mediated signaling and aggregation/secretion^21,51
						Potentiation of PAR-4–mediated aggregation¹²
						Mild bleeding diathesis⁶²
	Fgr	Human²⁰	Unknown	Unknown	αIIbβ3,²¹ GPVI-FcR γ-chain²¹	Marginal reduction in GPVI-mediated aggregation/secretion²¹
	Fgr	Mouse²¹	Unknown	Unknown	αIIbβ3,²¹ GPVI-FcR γ-chain²¹	Marginal reduction in GPVI-mediated aggregation/secretion²¹
SrcB	Lyn	Human¹⁷	GPVI,⁵⁰ β3,^25,45 GPIbα,⁷¹ PECAM-1,⁶⁰ SHIP-1⁴⁵	FcR γ-chain,^50,51 SHIP-1⁴⁵	αIIbβ3,^25,31,45 GPVI-FcR γ-chain,^50,51 PECAM-1,^13,60 GPIb-IX-V,¹⁰²	Increased αIIbβ3-mediated spreading^21,45
		Mouse⁵¹			PAR-1, PAR-4,^7,103 P2Y₁₂,⁷ Mpl⁵⁷	Delayed onset of GPVI-mediated signaling and aggregation/secretion^21,51
						Recovery of GPVI-mediated signaling and enhanced aggregation/secretion at later time points^21,51
						Reduced GPIb-IX-V–mediated spreading¹⁰²
						Increased megakaryopoiesis and Mpl signaling⁵⁷
						Cholesterol sensor in megakaryocyte progenitors⁵⁸
	Hck	Human⁶⁰	Unknown
	Lck	Human^19,20
	Blk	Not detected²¹
Src-related kinases	Frk	Unknown
	Brk	Unknown
	Srm	Unknown

Subfamily	Src kinase	Species	Interacting proteins	Substrates	Receptor signaling regulated by SFKs	Phenotypes of knockout mouse models
SrcA	Src	Human²⁶	β3,³¹ GPIbα,⁷¹ SHIP-1⁴⁴	β3,⁹⁵ FcγRIIA,⁴³ SHIP-1⁴⁴	αIIbβ3,^25,31,44 α2β1,⁹⁶ α6β1⁹⁷	Reduced αIlbβ3-mediated signaling and functional responses^21,31
	Src	Mouse^21,31	β3,³¹ GPIbα,⁷¹ SHIP-1⁴⁴	β3,⁹⁵ FcγRIIA,⁴³ SHIP-1⁴⁴	GPIb-IX-V,⁷¹ PAR-1, PAR-4,^6,83 TP,⁹⁸ α_2A⁹⁹
	Yes	Human^16,19	β3²⁵	Unknown	αIIbβ3,¹⁰⁰ PAR-1, PAR-4¹⁰¹
	Fyn	Human¹⁸	GPVI,⁵⁰ β3,⁶² PECAM-1⁶⁰	FcR γ-chain,^50,51 PKCδ⁷³	αIIbβ3,⁶² GPVI-FcR γ-chain,^50,51 GPIb-IX-V,⁷⁵ PAR-1, PAR-4,^7,12 P2Y₁₂⁷	Reduced unknown αIIbβ3-mediated signaling and functional responses^21,62
		Mouse⁵¹				Reduced GPVI-FcR γ-chain–mediated signaling and aggregation/secretion^21,51
						Potentiation of PAR-4–mediated aggregation¹²
						Mild bleeding diathesis⁶²
	Fgr	Human²⁰	Unknown	Unknown	αIIbβ3,²¹ GPVI-FcR γ-chain²¹	Marginal reduction in GPVI-mediated aggregation/secretion²¹
	Fgr	Mouse²¹	Unknown	Unknown	αIIbβ3,²¹ GPVI-FcR γ-chain²¹	Marginal reduction in GPVI-mediated aggregation/secretion²¹
SrcB	Lyn	Human¹⁷	GPVI,⁵⁰ β3,^25,45 GPIbα,⁷¹ PECAM-1,⁶⁰ SHIP-1⁴⁵	FcR γ-chain,^50,51 SHIP-1⁴⁵	αIIbβ3,^25,31,45 GPVI-FcR γ-chain,^50,51 PECAM-1,^13,60 GPIb-IX-V,¹⁰²	Increased αIIbβ3-mediated spreading^21,45
		Mouse⁵¹			PAR-1, PAR-4,^7,103 P2Y₁₂,⁷ Mpl⁵⁷	Delayed onset of GPVI-mediated signaling and aggregation/secretion^21,51
						Recovery of GPVI-mediated signaling and enhanced aggregation/secretion at later time points^21,51
						Reduced GPIb-IX-V–mediated spreading¹⁰²
						Increased megakaryopoiesis and Mpl signaling⁵⁷
						Cholesterol sensor in megakaryocyte progenitors⁵⁸
	Hck	Human⁶⁰	Unknown
	Lck	Human^19,20
	Blk	Not detected²¹
Src-related kinases	Frk	Unknown
	Brk	Unknown
	Srm	Unknown

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