A Small Fibronectin-mimicking Protein from Bacteria Induces Cell Spreading and Focal Adhesion Formation

Tegtmeyer N, Hartig R, Delahay RM, Rohde M, Brandt S, Conradi J, Takahashi S, Smolka AJ, Sewald N, Backert S (2010)
JOURNAL OF BIOLOGICAL CHEMISTRY 285(30): 23515-23526.

Journal Article | Published | English

No fulltext has been uploaded

Author
; ; ; ; ; ; ; ; ;
Abstract
Fibronectin, a 250-kDa eukaryotic extracellular matrix protein containing an RGD motif plays crucial roles in cell-cell communication, development, tissue homeostasis, and disease development. The highly complex fibrillar fibronectin meshwork orchestrates the functions of other extracellular matrix proteins, promoting cell adhesion, migration, and intracellular signaling. Here, we demonstrate that CagL, a 26-kDa protein of the gastric pathogen and type I carcinogen Helicobacter pylori, mimics fibronectin in various cellular functions. Like fibronectin, CagL contains a RGD motif and is located on the surface of the bacterial type IV secretion pili as previously shown. CagL binds to the integrin receptor alpha(5)beta(1) and mediates the injection of virulence factors into host target cells. We show that purified CagL alone can directly trigger intracellular signaling pathways upon contact with mammalian cells and can complement the spreading defect of fibronectin(-/-) knock-out cells in vitro. During interaction with various human and mouse cell lines, CagL mimics fibronectin in triggering cell spreading, focal adhesion formation, and activation of several tyrosine kinases in an RGD-dependent manner. Among the activated factors are the nonreceptor tyrosine kinases focal adhesion kinase and Src but also the epidermal growth factor receptor and epidermal growth factor receptor family member Her3/ErbB3. Interestingly, fibronectin activates a similar range of tyrosine kinases but not Her3/ErbB3. These findings suggest that the bacterial protein CagL not only exhibits functional mimicry with fibronectin but is also capable of activating fibronectin-independent signaling events. We thus postulate that CagL may contribute directly to H. pylori pathogenesis by promoting aberrant signaling crosstalk within host cells.
Publishing Year
ISSN
eISSN
PUB-ID

Cite this

Tegtmeyer N, Hartig R, Delahay RM, et al. A Small Fibronectin-mimicking Protein from Bacteria Induces Cell Spreading and Focal Adhesion Formation. JOURNAL OF BIOLOGICAL CHEMISTRY. 2010;285(30):23515-23526.
Tegtmeyer, N., Hartig, R., Delahay, R. M., Rohde, M., Brandt, S., Conradi, J., Takahashi, S., et al. (2010). A Small Fibronectin-mimicking Protein from Bacteria Induces Cell Spreading and Focal Adhesion Formation. JOURNAL OF BIOLOGICAL CHEMISTRY, 285(30), 23515-23526.
Tegtmeyer, N., Hartig, R., Delahay, R. M., Rohde, M., Brandt, S., Conradi, J., Takahashi, S., Smolka, A. J., Sewald, N., and Backert, S. (2010). A Small Fibronectin-mimicking Protein from Bacteria Induces Cell Spreading and Focal Adhesion Formation. JOURNAL OF BIOLOGICAL CHEMISTRY 285, 23515-23526.
Tegtmeyer, N., et al., 2010. A Small Fibronectin-mimicking Protein from Bacteria Induces Cell Spreading and Focal Adhesion Formation. JOURNAL OF BIOLOGICAL CHEMISTRY, 285(30), p 23515-23526.
N. Tegtmeyer, et al., “A Small Fibronectin-mimicking Protein from Bacteria Induces Cell Spreading and Focal Adhesion Formation”, JOURNAL OF BIOLOGICAL CHEMISTRY, vol. 285, 2010, pp. 23515-23526.
Tegtmeyer, N., Hartig, R., Delahay, R.M., Rohde, M., Brandt, S., Conradi, J., Takahashi, S., Smolka, A.J., Sewald, N., Backert, S.: A Small Fibronectin-mimicking Protein from Bacteria Induces Cell Spreading and Focal Adhesion Formation. JOURNAL OF BIOLOGICAL CHEMISTRY. 285, 23515-23526 (2010).
Tegtmeyer, Nicole, Hartig, Roland, Delahay, Robin M., Rohde, Manfred, Brandt, Sabine, Conradi, Jens, Takahashi, Seiichiro, Smolka, Adam J., Sewald, Norbert, and Backert, Steffen. “A Small Fibronectin-mimicking Protein from Bacteria Induces Cell Spreading and Focal Adhesion Formation”. JOURNAL OF BIOLOGICAL CHEMISTRY 285.30 (2010): 23515-23526.
This data publication is cited in the following publications:
This publication cites the following data publications:

35 Citations in Europe PMC

Data provided by Europe PubMed Central.

Mechanism and Function of Type IV Secretion During Infection of the Human Host.
Gonzalez-Rivera C, Bhatty M, Christie PJ., Microbiol Spectr 4(3), 2016
PMID: 27337453
Systematic analysis of phosphotyrosine antibodies recognizing single phosphorylated EPIYA-motifs in CagA of Western-type Helicobacter pylori strains.
Lind J, Backert S, Pfleiderer K, Berg DE, Yamaoka Y, Sticht H, Tegtmeyer N., PLoS ONE 9(5), 2014
PMID: 24800748
Potential of known and short prokaryotic protein motifs as a basis for novel peptide-based antibacterial therapeutics: a computational survey.
Ruhanen H, Hurley D, Ghosh A, O'Brien KT, Johnston CR, Shields DC., Front Microbiol 5(), 2014
PMID: 24478765
Mapping of p140Cap phosphorylation sites: the EPLYA and EGLYA motifs have a key role in tyrosine phosphorylation and Csk binding, and are substrates of the Abl kinase.
Repetto D, Aramu S, Boeri Erba E, Sharma N, Grasso S, Russo I, Jensen ON, Cabodi S, Turco E, Di Stefano P, Defilippi P., PLoS ONE 8(1), 2013
PMID: 23383002

69 References

Data provided by Europe PubMed Central.

Defining fibronectin's cell adhesion synergy site by site-directed mutagenesis.
Redick SD, Settles DL, Briscoe G, Erickson HP., J. Cell Biol. 149(2), 2000
PMID: 10769040
Binding and internalization of microorganisms by integrin receptors.
Isberg RR, Tran Van Nhieu G., Trends Microbiol. 2(1), 1994
PMID: 8162429
Induction of cell death in T lymphocytes by invasin via beta1-integrin.
Arencibia I, Frankel G, Sundqvist KG., Eur. J. Immunol. 32(4), 2002
PMID: 11932920
Specific entry of Helicobacter pylori into cultured gastric epithelial cells via a zipper-like mechanism.
Kwok T, Backert S, Schwarz H, Berger J, Meyer TF., Infect. Immun. 70(4), 2002
PMID: 11895977
cag+ Helicobacter pylori induce transactivation of the epidermal growth factor receptor in AGS gastric epithelial cells.
Keates S, Sougioultzis S, Keates AC, Zhao D, Peek RM Jr, Shaw LM, Kelly CP., J. Biol. Chem. 276(51), 2001
PMID: 11604402
Epidermal growth factor receptor activation protects gastric epithelial cells from Helicobacter pylori-induced apoptosis.
Yan F, Cao H, Chaturvedi R, Krishna U, Hobbs SS, Dempsey PJ, Peek RM Jr, Cover TL, Washington MK, Wilson KT, Polk DB., Gastroenterology 136(4), 2009
PMID: 19250983
EGF receptor transactivation by G-protein-coupled receptors requires metalloproteinase cleavage of proHB-EGF.
Prenzel N, Zwick E, Daub H, Leserer M, Abraham R, Wallasch C, Ullrich A., Nature 402(6764), 1999
PMID: 10622253
Helicobacter pylori-stimulated EGF receptor transactivation requires metalloprotease cleavage of HB-EGF.
Wallasch C, Crabtree JE, Bevec D, Robinson PA, Wagner H, Ullrich A., Biochem. Biophys. Res. Commun. 295(3), 2002
PMID: 12099696
Helicobacter pylori-stimulated interleukin-8 (IL-8) promotes cell proliferation through transactivation of epidermal growth factor receptor (EGFR) by disintegrin and metalloproteinase (ADAM) activation.
Joh T, Kataoka H, Tanida S, Watanabe K, Ohshima T, Sasaki M, Nakao H, Ohhara H, Higashiyama S, Itoh M., Dig. Dis. Sci. 50(11), 2005
PMID: 16240219
A novel sheathed surface organelle of the Helicobacter pylori cag type IV secretion system.
Rohde M, Puls J, Buhrdorf R, Fischer W, Haas R., Mol. Microbiol. 49(1), 2003
PMID: 12823823
FAK integrates growth-factor and integrin signals to promote cell migration.
Sieg DJ, Hauck CR, Ilic D, Klingbeil CK, Schaefer E, Damsky CH, Schlaepfer DD., Nat. Cell Biol. 2(5), 2000
PMID: 10806474

Export

0 Marked Publications

Open Data PUB

Web of Science

View record in Web of Science®

Sources

PMID: 20507990
PubMed | Europe PMC

Search this title in

Google Scholar