Yersinia type III effectors perturb host innate immune responses

Table 1 The Yersinia effector proteins, their host substrates, and cellular effects

Yop effectors	Enzymatic function	Target substrates	Cellular effects
YpkA/YopO	Serine/threonine kinase	Gαq, EVL, VASP, WASP, WIP, gelsolin, mDia1, INF2, and cofilin	Disruption of the actin cytoskeleton to contribute to inhibition of phagocytosis; additional effects are unknown
	Guanine nucleotide dissociation-like inhibitor	RhoA, Rac1, and Rac2	Disruption of the actin cytoskeleton to contribute to inhibition of phagocytosis
YopE	GTPase activating protein	RhoA, Cdc42, Rac2, and RhoG	Disruption of the actin cytoskeleton to contribute to inhibition of phagocytosis; inhibition of caspase-1 activation and maturation of IL-18 and IL-1β
YopH	Protein tyrosine phosphatase	FAK, p130Cas, paxillin, Fyb, SKAP-HOM, PRAM-1, SLP-76, Vav, PLCγ2, p85, Gab1, Gab2, Lck, and LAT	Disruption of focal adhesion complexes and actin stress fibers to inhibit phagocytosis; inhibition of proinflammatory cytokine and MCP-1 production; inhibition of early calcium response and ROS production; inhibition of the PI3K/Akt pathway
YopP/J	Acetyltransferase/cysteine protease/deubiquintase	TRAF2, TRAF6, IκBα, MAPKKKs, MAPKKs, IKKβ, RICK, and eIF2α	Inhibition of adhesion molecules, proinflammatory cytokine and chemokine production; activation of caspase-1 and maturation of IL-18 and IL-1β; induction of apoptosis
YopT	Cysteine protease	RhoA, Rac1, Cdc42, and RhoG	Disruption of the actin cytoskeleton to contribute to inhibition of phagocytosis; inhibition of NFκB
YopM	Leucine-rich repeat protein	RSK and PRK isoforms, caspase-1, and IQGAP1	Inhibition of proinflammatory cytokine production; inhibition of caspase-1 activation; induction of apoptosis; induction of anti-inflammatory cytokine production

IL: Interleukin; FAK: Focal adhesion kinase; PLC-γ2: Phospholipase C-γ2; MAPK: Mitogen-activated protein kinase; MAPKK: MAPK kinase; MAPKKK: MAPKK kinase; Akt: Protein kinase B; NFκB: Nuclear factor kappa b; IKKβ: Inhibitor of kappa B kinase beta; IκBα: Inhibitor of kappa B alpha; IQGAP1: IQ motif containing GTPase activating protein 1; Lck: Lymphocyte-specific protein tyrosine kinase; LAT: Linker for activation of T cell; eIF2α: Eukaryotic initiation factor 2; PRK: Protein kinase C-related kinase; RSK: Ribosomal S6 protein kinase; VASP: Vasodilator-stimulated phosphoprotein; WASP: Wiskott-Aldrich syndrome protein; WIP: WASP-interacting protein; p130_Cas: Crk associated tyrosine kinase substrate; Fyb: Fyn-binding protein; SKAP-HOM: Src kinase-associated phosphoprotein 55 homologue; PRAM-1: PML-retinoic acid receptor alpha regulated adaptor molecule 1; SLP-76: SH2 domain containing leukocyte protein of 76 kDa; EVL: Ena/VASP-like; INF2: Inverted formin 2; TRAF: TNF-receptor associated factor; RICK: Rip-like interacting caspase-like apoptosis-regulatory protein kinase; MCP-1: Monocyte chemotactic protein 1; ROS: Reactive oxygen species; PI3K: Phosphatidylinositol 3-kinase; mDia1: Mammalian diaphanous 1; Gab: Grb-associated-binder.