T4SS ID	4
Strain	Helicobacter pylori 26695
Replicon	chromosome [Browse all T4SS(s) in this replicon]
Accession	NC_000915
Location	548134..579087
Name	Cag
Function	effector translocation
Classification	Type IVA; Type P
Experimental investigation has been performed on this T4SS.

Information of structure: CagY, CagD, Outer membrane core complex (OMCC), HP0525, CagT, HP0525 bound by sulfate, VirB11, CagA Inhibits PAR1/MARK Family Kinases, CagX, CagS, CagZ, VirB11-like protein in complex with ATPgammaS, CagL, N-terminal domain of CagA, Periplasmic ring complex (PRC), Cag T4SS, CagA, CagA Oncogene Bound to the Human Tumor Suppressor Apoptosis-stimulating Protein of p53-2

T4SS components

Component	CagC	CagD	CagE	CagF	CagG	CagH	CagI	CagL	CagN
Number	1	1	1	1	1	1	1	1	1
Component	CagM	CagT	CagU	CagV	CagW	CagX	CagY	CagZ	Cagalpha
Number	1	1	1	1	1	1	1	1	1
Component	Cagbeta	Caggamma	Cagdelta
Number	1	1	1

The information of T4SS components from NC_000915
#	Locus tag (Gene)	Coordinates [+/-], size (bp)	Protein GI	Product	Component
1	HP0517 (era)	544336..545244 [+], 909	15645144	GTP-binding protein Era
2	HP0518	545241..546233 [+], 993	15645145	hypothetical protein
3	HP0519	546322..547152 [-], 831	15645146	hypothetical protein
4	HP0520	547328..547675 [+], 348	15645147	cag pathogenicity island protein (cag1)
5	HP0522	548134..549579 [+], 1446	15645148	cag pathogenicity island protein (cag3)	Cagdelta
6	HP0523	549589..550098 [+], 510	15645149	cag pathogenicity island protein (cag4)	Caggamma
7	HP0524	550217..552463 [-], 2247	15645150	cag pathogenicity island protein (cag5)	Cagbeta
8	HP0525	552472..553464 [-], 993	15645151	virB11-like protein	Cagalpha
9	HP0526	553469..554068 [-], 600	15645152	cag pathogenicity island protein (cag6)	CagZ
10	HP0527	554206..559989 [-], 5784	15645153	cag pathogenicity island protein (cag7)	CagY
11	HP0528	560004..561572 [-], 1569	15645154	cag pathogenicity island protein (cag8)	CagX
12	HP0529	561625..563232 [-], 1608	15645155	cag pathogenicity island protein (cag9)	CagW
13	HP0530	563237..563995 [-], 759	15645156	cag pathogenicity island protein (cag10)	CagV
14	HP0531	564381..565037 [+], 657	15645157	cag pathogenicity island protein (cag11)	CagU
15	HP0532	565073..565915 [+], 843	15645158	cag pathogenicity island protein (cag12)	CagT
16	HP0534	566126..566716 [-], 591	15645160	cag pathogenicity island protein (cag13)
17	HP0535	567142..567522 [-], 381	15645161	cag pathogenicity island protein (cag14)
18	HP0536	567955..568299 [-], 345	15645162	cag pathogenicity island protein (cag15)
19	HP0537	568723..569853 [+], 1131	15645163	cag pathogenicity island protein (cag16)	CagM
20	HP0538	569868..570788 [+], 921	15645164	cag pathogenicity island protein (cag17)	CagN
21	HP0539	570870..571583 [-], 714	15645165	cag pathogenicity island protein (cag18)	CagL
22	HP0540	571580..572725 [-], 1146	15645166	cag pathogenicity island protein (cag19)	CagI
23	HP0541	572736..573848 [-], 1113	15645167	cag pathogenicity island protein (cag20)	CagH
24	HP0542	573864..574292 [-], 429	15645168	cag pathogenicity island protein (cag21)	CagG
25	HP0543	574347..575153 [-], 807	15645169	cag pathogenicity island protein (cag22)	CagF
26	HP0544	575155..578106 [-], 2952	15645170	cag pathogenicity island protein (cag23)	CagE
27	HP0545	578115..578738 [-], 624	15645171	cag pathogenicity island protein (cag24)	CagD
28	HP0546	578740..579087 [-], 348	15645172	cag pathogenicity island protein (cag25)	CagC
29	HP0547	579921..583481 [+], 3561	15645173	cag pathogenicity island protein (cag26)

 This T4SS contains information of accessory protein.
 This T4SS contains information of interaction.

Genes in the 5-Kb flanking regions if available, or non-essential genes in the T4SS gene cluster if any.

Download FASTA format files

Proteins        Genes

As a consequence of CagA action, epithelial cells will have some of their major functions disturbed, such as cell-cell adhesion, signalling, adherence and proliferation

Effectors

CagA; Peptidoglycan

The information of protein effectors
#	Locus tag (Gene)	Coordinates [+/-], size (bp)	Protein GI	Product	*
1	HP0547	579921..583481 [+], 3561	15645173	cag pathogenicity island protein (cag26)	CagA

 T4SE derived from experimental literature.
 This effector contains information of interaction.

Download FASTA format files

Proteins        Genes

The information on structure of this T4ss

#	Name	Image	Resource	Detail	Reference
1	CagA		PDB (4DVY)	Crystal structure of the Helicobacter pylori CagA oncoprotein.	(1) PubMed: 22817985
2	CagA		PDB (4DVZ)	Crystal structure of the Helicobacter pylori CagA oncoprotein.	(2) PubMed: 22817985
3	CagA Inhibits PAR1/MARK Family Kinases		PDB (3IEC)	Helicobacter pylori CagA Inhibits PAR1/MARK Family Kinases by Mimicking Host Substrates.	(3) PubMed: 19966800
4	CagA Oncogene Bound to the Human Tumor Suppressor Apoptosis-stimulating Protein of p53-2		PDB (4IRV)	Structure of the Helicobacter pylori CagA Oncogene Bound to the Human Tumor Suppressor Apoptosis-stimulating Protein of p53-2.	(4) PubMed: 24474782
5	CagD		PDB (3CWX)	Crystal structure of cagd from helicobacter pylori pathogenicity island.	(5) PubMed: 19109970
6	CagL		PDB (3ZCJ)	Crystal structure of Helicobacter pylori T4SS protein CagL in a tetragonal crystal form with a helical RGD-motif (6 Mol per ASU).	(6) PubMed: 24076404
7	CagL		PDB (3ZCI)	Crystal structure of Helicobacter pylori T4SS protein CagL in a cubic crystal form with a distorted helical conformation of the RGD-motif.	(7) PubMed: 24076404
8	CagL		PDB (4X5U)	X-ray crystal structure of CagL at pH 4.2.	(8) PubMed: 25837254
9	CagS		PDB (2G3V)	Crystal structure of CagS (HP0534, Cag13) from Helicobacter pylori.	(9) PubMed: 17623849
10	CagT		PDB (6OEE)	Structure of CagT from a cryo-EM reconstruction of a T4SS.	(10) PubMed: 31210639
11	Cag T4SS		EMDB(7474)	Subtomogram average of the cag type IV secretion system in Helicobacter pylori cells (aligning periplasmic parts).	(11) PubMed: 29669273
12	CagX		PDB (5H3V)	Crystal structure of a Type IV Secretion System Component CagX in Helicobacter pylori.	(12) PubMed: 28291753
13	CagX		PDB (6OEG)	Structure of CagX from a cryo-EM reconstruction of a T4SS	(13) PubMed: 31210639
14	CagY		PDB (6ODI)	Structure of CagY from a cryo-EM reconstruction of a T4SS.	(14) PubMed: 31210639
15	CagY		PDB (6OEF)	Structure of CagY from a cryo-EM reconstruction of a T4SS.	(15) PubMed: 31210639
16	CagZ		PDB (1S2X)	Crystal structure of Cag-Z from Helicobacter pylori.	(16) PubMed: 15223328
17	HP0525		PDB (1G6O)	Crystal structure of the helicobacter pylori ATPase, HP0525, in complex with ADP.	(17) PubMed: 11163218
18	HP0525 bound by sulfate		PDB (1OPX)	Crystal structure of the traffic ATPase (HP0525) of the Helicobacter pylori type IV secretion system bound by sulfate.	(18) PubMed: 12727865
19	N-terminal domain of CagA		PDB (4G0H)	Crystal structure of the N-terminal domain of Helicobacter pylori CagA protein.	(19) PubMed: 22908298
20	Outer membrane core complex (OMCC)		PDB (6OEH)	PolyAla Model of OMCC I-Layer.	(20) PubMed: 31210639
21	Outer membrane core complex (OMCC)		EMDB(20023)	Reconstruction of a T4SS OMCC.	(21) PubMed: 31210639
22	Outer membrane core complex (OMCC)		EMDB(20020)	Reconstruction of a T4SS OMCC.	(22) PubMed: 31210639
23	Outer membrane core complex (OMCC)		EMDB(20022)	Reconstruction of a T4SS OMCC.	(23) PubMed: 31210639
24	Periplasmic ring complex (PRC)		PDB (6ODJ)	PolyAla Model of the PRC from the Type 4 Secretion System of H. pylori.	(24) PubMed: 31210639
25	Periplasmic ring complex (PRC)		EMDB(20021)	PolyAla Model of the PRC from the Type 4 Secretion System of H. pylori.	(25) PubMed: 31210639
26	VirB11		PDB (1NLZ )	Crystal structure of unliganded traffic ATPase of the type IV secretion system of helicobacter pylori.	(26) PubMed: 12727865
27	VirB11-like protein in complex with ATPgammaS		PDB (1NLY)	Crystal structure of the traffic ATPase of the Helicobacter pylori type IV secretion system in complex with ATPgammaS.	(27) PubMed: 25825348

(1) Hayashi T et al. (2012). Tertiary structure-function analysis reveals the pathogenic signaling potentiation mechanism of Helicobacter pylori oncogenic effector CagA. Cell Host Microbe. 12(1):20-33. [PudMed:22817985]

(2) Hayashi T et al. (2012). Tertiary structure-function analysis reveals the pathogenic signaling potentiation mechanism of Helicobacter pylori oncogenic effector CagA. Cell Host Microbe. 12(1):20-33. [PudMed:22817985]

(3) Nesić D et al. (2010). Helicobacter pylori CagA inhibits PAR1-MARK family kinases by mimicking host substrates. Nat Struct Mol Biol. 17(1):130-2. [PudMed:19966800]

(4) Nešić D et al. (2014). Structure of the Helicobacter pylori CagA oncoprotein bound to the human tumor suppressor ASPP2. Proc Natl Acad Sci U S A. 111(4):1562-7. [PudMed:24474782]

(5) Cendron L; Couturier M; Angelini A; Barison N; Stein M; Zanotti G (2009). The Helicobacter pylori CagD (HP0545, Cag24) protein is essential for CagA translocation and maximal induction of interleukin-8 secretion. J Mol Biol. 386(1):204-17. [PudMed:19109970]

(6) Barden S et al. (2013). A helical RGD motif promoting cell adhesion: crystal structures of the Helicobacter pylori type IV secretion system pilus protein CagL. Structure. 21(11):1931-41. [PudMed:24076404]

(7) Barden S et al. (2013). A helical RGD motif promoting cell adhesion: crystal structures of the Helicobacter pylori type IV secretion system pilus protein CagL. Structure. 21(11):1931-41. [PudMed:24076404]

(8) Bonsor DA et al. (2015). Integrin engagement by the helical RGD motif of the Helicobacter pylori CagL protein is regulated by pH-induced displacement of a neighboring helix. J Biol Chem. 290(20):12929-40. [PudMed:25837254]

(9) Cendron L et al. (2007). The crystal structure of CagS from the Helicobacter pylori pathogenicity island. Proteins. 69(2):440-3. [PudMed:17623849]

(10) Chung JM et al. (2019). Structure of the Helicobacter pylori Cag type IV secretion system. Elife. 8. pii: e47644. [PudMed:31210639]

(11) Chang YW et al. (2018). In Vivo Structures of the Helicobacter pylori cag Type IV Secretion System. Cell Rep. 23(3):673-681. [PudMed:29669273]

(12) Zhang J et al. (2017). Crystal structure of the type IV secretion system component CagX from Helicobacter pylori. Acta Crystallogr F Struct Biol Commun. 73(Pt 3):167-173. [PudMed:28291753]

(13) Chung JM et al. (2019). Structure of the Helicobacter pylori Cag type IV secretion system. Elife. 8. pii: e47644. [PudMed:31210639]

(14) Chung JM et al. (2019). Structure of the Helicobacter pylori Cag type IV secretion system. Elife. 8. pii: e47644. [PudMed:31210639]

(15) Chung JM et al. (2019). Structure of the Helicobacter pylori Cag type IV secretion system. Elife. 8. pii: e47644. [PudMed:31210639]

(16) Cendron L; Seydel A; Angelini A; Battistutta R; Zanotti G (2004). Crystal structure of CagZ, a protein from the Helicobacter pylori pathogenicity island that encodes for a type IV secretion system. J Mol Biol. 340(4):881-9. [PudMed:15223328]

(17) Yeo HJ; Savvides SN; Herr AB; Lanka E; Waksman G (2000). Crystal structure of the hexameric traffic ATPase of the Helicobacter pylori type IV secretion system. Mol Cell. 6(6):1461-72. [PudMed:11163218]

(18) Savvides SN; Yeo HJ; Beck MR; Blaesing F; Lurz R; Lanka E; Buhrdorf R; Fischer W; Haas R; Waksman G (2003). VirB11 ATPases are dynamic hexameric assemblies: new insights into bacterial type IV secretion. EMBO J. 22(9):1969-80. [PudMed:12727865]

(19) Kaplan-Türköz B et al. (2012). Structural insights into Helicobacter pylori oncoprotein CagA interaction with β1 integrin. Proc Natl Acad Sci U S A. 109(36):14640-5. [PudMed:22908298]

(20) Chung JM et al. (2019). Structure of the Helicobacter pylori Cag type IV secretion system. Elife. 8. pii: e47644. [PudMed:31210639]

(21) Chung JM et al. (2019). Structure of the Helicobacter pylori Cag type IV secretion system. Elife. 8. pii: e47644. [PudMed:31210639]

(22) Chung JM et al. (2019). Structure of the Helicobacter pylori Cag type IV secretion system. Elife. 8. pii: e47644. [PudMed:31210639]

(23) Chung JM et al. (2019). Structure of the Helicobacter pylori Cag type IV secretion system. Elife. 8. pii: e47644. [PudMed:31210639]

(24) Chung JM et al. (2019). Structure of the Helicobacter pylori Cag type IV secretion system. Elife. 8. pii: e47644. [PudMed:31210639]

(25) Chung JM et al. (2019). Structure of the Helicobacter pylori Cag type IV secretion system. Elife. 8. pii: e47644. [PudMed:31210639]

(26) Savvides SN; Yeo HJ; Beck MR; Blaesing F; Lurz R; Lanka E; Buhrdorf R; Fischer W; Haas R; Waksman G (2003). VirB11 ATPases are dynamic hexameric assemblies: new insights into bacterial type IV secretion. EMBO J. 22(9):1969-80. [PudMed:12727865]

(27) Ilangovan A et al. (2015). Structural biology of the Gram-negative bacterial conjugation systems. Trends Microbiol. 23(5):301-10. [PudMed:25825348]

The information on requirements for T4SS substrate-channel docking

Certain T4SS substrates require secretion chaperones for translocation. These chaperones often possess physical properties (small size of 15 kDa, acidic pI, and amphipathic helices) resembling those of chaperones associated with the type III secretion systems, a family of macromolecular translocation systems ancestrally related to bacterial flagella.

#	Accessory protein(GI)	motif(s)	Substrate(s)	Function	Reference
1	CagF (chaperone) (15645169)	CT20aa and an intact N terminus	CagA	The CagA-binding protein CagF is a secretion chaperone-like protein that interacts with a region that is adjacent to the C-terminal secretion signal of CagA.	(1) PubMed: 17768234

Tips:
1.Substrate(s): For the conjugation systems, the listed proteins are relaxases that bind a cognate T4CP and are delivered to recipient cells. For the effector translocator systems, the listed proteins are effectors that play a role in the infection processes of the bacterial pathogen.
2.motif(s):The motifs listed are required for substrate translocation. In some cases, the protein or its C-terminal fragment (CT) is sufficient to mediate translocation to target cells, as shown by fusion to a reporter protein such as Cre recombinase or adenylate cyclase. Amino acids (aa) at positions listed relative to the C-terminal fragment (subscript) are required for translocation, as shown by mutational analysis. ND, not determined. Parentheses indicate that the interaction between a protein substrate and a cognate T4CP has been experimentally shown.
3.Accessory protein: Accessory factors required for T4SS channel docking or translocation. The proposed function in mediating substrate-T4SS channel docking is shown in parentheses.PubMed:19946141

(1) Pattis I; Weiss E; Laugks R; Haas R; Fischer W (2007). The Helicobacter pylori CagF protein is a type IV secretion chaperone-like molecule that binds close to the C-terminal secretion signal of the CagA effector protein. Microbiology. 153(Pt 9):2896-909. [PudMed:17768234]

The information on host-pathogen interaction.

#	Name(Protein GI)	Host site/Substrate	Source	Function	Reference
1	CagA (15645173)	SHP-2	human	CagA is translocated into gastric epithelial cells. It physically interacts with SHP-2 to modify cellular functions and perturb mammalian signal transduction machineries. This may induce gastric epithelial cells to move and proliferate abnormally and help to acquire a cellular transformed phenotype.	(1) PubMed: 11743164
2	CagA (15645173)	growth factor receptor bound 2 (Grb2)	unknown	CagA targets to Grb2 and this process leads to activing the MEK/ERK pathway and results in cell scattering and proliferation.	(2) PubMed: 12419219
3	CagA (15645173)	PAR1/MARK kinase	human	CagA interacts with PAR1/MARK kinase to inhibit the activity of PAR1 kinase and prevent PAR1 phosphorylation which mediated by atypical protein kinase C (aPKC).	(3) PubMed: 17507984
4	CagA (15645173)	Apoptosis-stimulating of p53 protein 2 (ASPP2)	human	ASPP2 is a tumor suppressor that activates the apoptotic response upon cellular stress which mediated by p53. CagA interacts with ASPP2 to change the function of ASPP2 and this process leads to the decreased survival of cells which infected by H. pylori.	(4) PubMed: 24474782
5	CagA (15645173)	protein kinase C-related kinase 2 (PRK2)	human	CagA represses kinase activity of PRK2, which has been involved in establishment of cell polarity and rearrangements of cytoskeleton, to further control signalling pathways associated with cancer.	(5) PubMed: 26041307
6	CagA (15645173)	Glycogen synthase kinase 3 (GSK-3)	human	CagA interacts with GSK-3 to reduce its activity by cause it to transform into an insoluble fraction. CagA then induce a epithelial mesenchymal transition mediated by Snail via the comsuming of GSK-3.	(6) PubMed: 25055241
7	CagA (15645173)	c-Met	human	CagA interacts with the c-Met receptor to modulates cellular functions through deregulating c-Met receptor signaling and participates in invasive growth of tumor cells.	(7) PubMed: 12719469
8	CagA (15645173)	E-cadherin	human	CagA interacts with E-cadherin to impair the complex formation between E-cadherin and beta-catenin and facilitate transdifferentiation of intestines in gastric epithelial cells.	(8) PubMed: 17237808
9	CagA (15645173)	host membrane phosphatidylserine	unknown	CagA can be tethered to the inner leaflet of the plasma membrane by interacting with phosphatidylserine. Then it binds the PAR1/MARK to induce polarity and junctional defects.	(9) PubMed: 20478541
10	CagA (15645173)	c-Abl tyrosine kinase	human	CagA targets to c-Abl directly and localizes in focal adhesion complexes and membrane ruffles.	(10) PubMed: 17160020
11	CagA (15645173)	αPix	human	CagA interacted with αPix to activates PAK1, ERK and NF-kappaB after being delivered into AGS cells. Then it induces the expression of IL-8 in infected gastric epithelial cells.	(11) PubMed: 19672789
12	CagA (15645173)	scaffolding protein ZO-1	human, canine	CagA interacts with epithelial tight-junction ZO-1 and the transmembrane protein junctional adhesion molecule to change the function and composition of the apical-junctional complex.	(12) PubMed: 12775840
13	CagA (15645173)	integrin α5β1 receptor	human	CagA binds interface with α5β1 integrin.It is an essential step for the translocation process of CagA into the host cell.	(13) PubMed: 22908298
14	CagA (15645173)	TNF receptor-associated factor 1 and 4-1BB (TRAF1 and 4-1BB)	human	CagA facilitates the proliferation and represses the apoptosis of GES-1 cells by upregulated TRAF1/4-1BB.	(14) PubMed: 28627614
15	CagA (15645173)	Adapter molecule crk	human	The interaction between CagA and Crk adaptor proteins is important for loss of gastric epithelial cell adhesion induced by Helicobacter pylori-induced Helicobacter pylori.	(15) PubMed: 16275761
16	CagA (15645173)	SHP-1	human	CagA interacts with SHP1 to enhance the phosphatase activity of SHP1 so that it dampens the oncogenic action of CagA.	(16) PubMed: 27572445
17	CagA (15645173)	Transforming growth factor-beta-activated kinase 1 (TAK1)	human	CagA interacts with TAK1 and improves its activity to activate NF-kappaB through the ubiquitination of TAK1.	(17) PubMed: 19820695
18	CagA (15645173)	Myeloid cell leukemia sequence-1 (MCL1)	mongolian gerbil	CagA increases MCL1 thorough the interaction between SRE/SRF and CagA/MCL1 in modulating rapid turnover of pit epithelial cells via MEK/ERK/SRE activation.	(18) PubMed: 18005743
19	CagL (15645165)	integrin α5β1 receptor	human	CagL, which is targeted to the pilus surface, is a specialized adhesin. It binds to and activates integrin α5β1 receptor on gastric epithelial cells. This interaction triggers CagA delivery into target cells.	(19) PubMed: 17943123
20	CagL (15645165)	integrin αvβ5	human	CagL/integrin β5 signalling complex is important for gastrin expression induced by H. pylori.	(20) PubMed: 22287591
21	CagL (15645165)	integrin αvβ3	human	Host cell docking of T4SS.	(21) PubMed: 21915696
22	CagL (15645165)	integrin αvβ6	human	αvβ6 is a specific, high affinity receptor for CagL.	(22) PubMed: 31197920
23	CagY (15645153)	integrin α5β1 receptor	human	CagY interacts with α5β1 integrin, which acts like a molecular rheostat that modulates the host immune response to facilitate persistent infection.	(23) PubMed: 29764950

This T4SE is mentioned in the literature.
This T4SE is highly identical with the protein mentioned in the literature.

(1) Higashi H et al. (2002). SHP-2 tyrosine phosphatase as an intracellular target of Helicobacter pylori CagA protein. Science. 295(5555):683-6. [PudMed:11743164]

(2) Mimuro H et al. (2002). Grb2 is a key mediator of helicobacter pylori CagA protein activities. Mol Cell. 10(4):745-55. [PudMed:12419219]

(3) Saadat I et al. (2007). Helicobacter pylori CagA targets PAR1/MARK kinase to disrupt epithelial cell polarity. Nature. 447(7142):330-3. [PudMed:17507984]

(4) Nešić D et al. (2014). Structure of the Helicobacter pylori CagA oncoprotein bound to the human tumor suppressor ASPP2. Proc Natl Acad Sci U S A. 111(4):1562-7. [PudMed:24474782]

(5) Mishra JP et al. (2015). CagA of Helicobacter pylori interacts with and inhibits the serine-threonine kinase PRK2. Cell Microbiol. 17(11):1670-82. [PudMed:26041307]

(6) Lee DG et al. (2014). Helicobacter pylori CagA promotes Snail-mediated epithelial-mesenchymal transition by reducing GSK-3 activity. Nat Commun. 5:4423. [PudMed:25055241]

(7) Churin Y et al. (2003). Helicobacter pylori CagA protein targets the c-Met receptor and enhances the motogenic response. J Cell Biol. 161(2):249-55. [PudMed:12719469]

(8) Murata-Kamiya N et al. (2007). Helicobacter pylori CagA interacts with E-cadherin and deregulates the beta-catenin signal that promotes intestinal transdifferentiation in gastric epithelial cells. Oncogene. 26(32):4617-26. [PudMed:17237808]

(9) Murata-Kamiya N; Kikuchi K; Hayashi T; Higashi H; Hatakeyama M (2010). Helicobacter pylori exploits host membrane phosphatidylserine for delivery, localization, and pathophysiological action of the CagA oncoprotein. Cell Host Microbe. 7(5):399-411. [PudMed:20478541]

(10) Poppe M; Feller SM; Romer G; Wessler S (2007). Phosphorylation of Helicobacter pylori CagA by c-Abl leads to cell motility. Oncogene. 26(24):3462-72. [PudMed:17160020]

(11) Lim JW et al. (2009). alphaPix interacts with Helicobacter pylori CagA to induce IL-8 expression in gastric epithelial cells. Scand J Gastroenterol. 44(10):1166-72. [PudMed:19672789]

(12) Amieva MR et al. (2003). Disruption of the epithelial apical-junctional complex by Helicobacter pylori CagA. Science. 300(5624):1430-4. [PudMed:12775840]

(13) Kaplan-Türköz B et al. (2012). Structural insights into Helicobacter pylori oncoprotein CagA interaction with β1 integrin. Proc Natl Acad Sci U S A. 109(36):14640-5. [PudMed:22908298]

(14) Wang F et al. (2017). CagA promotes proliferation and inhibits apoptosis of GES-1 cells by upregulating TRAF1/4-1BB. Mol Med Rep. 16(2):1262-1268. [PudMed:28627614]

(15) Suzuki M et al. (2005). Interaction of CagA with Crk plays an important role in Helicobacter pylori-induced loss of gastric epithelial cell adhesion. J Exp Med. 202(9):1235-47. [PudMed:16275761]

(16) Saju P et al. (2016). Host SHP1 phosphatase antagonizes Helicobacter pylori CagA and can be downregulated by Epstein-Barr virus. Nat Microbiol. 1:16026. [PudMed:27572445]

(17) Lamb A et al. (2009). Helicobacter pylori CagA activates NF-kappaB by targeting TAK1 for TRAF6-mediated Lys 63 ubiquitination. EMBO Rep. 10(11):1242-9. [PudMed:19820695]

(18) Mimuro H et al. (2007). Helicobacter pylori dampens gut epithelial self-renewal by inhibiting apoptosis, a bacterial strategy to enhance colonization of the stomach. Cell Host Microbe. 2(4):250-63. [PudMed:18005743]

(19) Kwok T; Zabler D; Urman S; Rohde M; Hartig R; Wessler S; Misselwitz R; Berger J; Sewald N; Konig W; Backert S (2007). Helicobacter exploits integrin for type IV secretion and kinase activation. Nature. 449(7164):862-6. [PudMed:17943123]

(20) Wiedemann T et al. (2012). Helicobacter pylori CagL dependent induction of gastrin expression via a novel αvβ5-integrin-integrin linked kinase signalling complex. Gut. 61(7):986-96. [PudMed:22287591]

(21) Conradi J; Huber S; Gaus K; Mertink F; Royo Gracia S; Strijowski U; Backert S; Sewald N (2012). Cyclic RGD peptides interfere with binding of the Helicobacter pylori protein CagL to integrins alpha(V)beta (3) and alpha (5)beta (1). Amino Acids. 43(1):219-32. [PudMed:21915696]

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