TY  - JOUR
A1  - Young, Joanna C.
A1  - Clements, Abigail
A1  - Lang, Alexander E.
A1  - Garnett, James A.
A1  - Munera, Diana
A1  - Arbeloa, Ana
A1  - Pearson, Jaclyn
A1  - Hartland, Elizabeth L.
A1  - Matthews, Stephen J.
A1  - Mousnier, Aurelie
A1  - Barry, David J.
A1  - Way, Michael
A1  - Schlosser, Andreas
A1  - Aktories, Klaus
A1  - Frankel, Gad
T1  - The Escherichia coli effector EspJ blocks Src kinase activity via amidation and ADP ribosylation
JF  - Nature Communications
N2  - The hallmark of enteropathogenic Escherichia coli (EPEC) infection is the formation of actin-rich pedestal-like structures, which are generated following phosphorylation of the bacterial effector Tir by cellular Src and Abl family tyrosine kinases. This leads to recruitment of the Nck-WIP-N-WASP complex that triggers Arp2/3-dependent actin polymerization in the host cell. The same phosphorylation-mediated signalling network is also assembled downstream of the Vaccinia virus protein A36 and the phagocytic Fc-gamma receptor FcγRIIa. Here we report that the EPEC type-III secretion system effector EspJ inhibits autophosphorylation of Src and phosphorylation of the Src substrates Tir and FcγRIIa. Consistent with this, EspJ inhibits actin polymerization downstream of EPEC, Vaccinia virus and opsonized red blood cells. We identify EspJ as a unique adenosine diphosphate (ADP) ribosyltransferase that directly inhibits Src kinase by simultaneous amidation and ADP ribosylation of the conserved kinase-domain residue, Src E310, resulting in glutamine-ADP ribose.
Y1  - 2014
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-121157
VL  - 5
IS  - 5887
ER  - 
TY  - JOUR
A1  - Schwan, Carsten
A1  - Lang, Alexander E.
A1  - Schlosser, Andreas
A1  - Fujita-Becker, Setsuko
A1  - AlHaj, Abdulatif
A1  - Schröder, Rasmus R.
A1  - Faix, Jan
A1  - Aktories, Klaus
A1  - Mannherz, Hans Georg
T1  - Inhibition of Arp2/3 complex after ADP-ribosylation of Arp2 by binary Clostridioides toxins
JF  - Cells
N2  - Clostridioides bacteria are responsible for life threatening infections. Here, we show that in addition to actin, the binary toxins CDT, C2I, and Iota from Clostridioides difficile, botulinum, and perfrigens, respectively, ADP-ribosylate the actin-related protein Arp2 of Arp2/3 complex and its additional components ArpC1, ArpC2, and ArpC4/5. The Arp2/3 complex is composed of seven subunits and stimulates the formation of branched actin filament networks. This activity is inhibited after ADP-ribosylation of Arp2. Translocation of the ADP-ribosyltransferase component of CDT toxin into human colon carcinoma Caco2 cells led to ADP-ribosylation of cellular Arp2 and actin followed by a collapse of the lamellipodial extensions and F-actin network. Exposure of isolated mouse colon pieces to CDT toxin induced the dissolution of the enterocytes leading to luminal aggregation of cellular debris and the collapse of the mucosal organization. Thus, we identify the Arp2/3 complex as hitherto unknown target of clostridial ADP-ribosyltransferases.
KW  - actin
KW  - ADP-ribosyltransferases
KW  - Arp2/3 complex
KW  - Clostridioides binary toxins
Y1  - 2022
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-297454
SN  - 2073-4409
VL  - 11
IS  - 22
ER  -