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Fyn binding protein, Fyb, interacts with mammalian actin binding protein, mAbp1.
Umeå universitet, Medicinsk fakultet, Molekylärbiologi (Medicinska fakulteten). (Fällman)
Umeå universitet, Medicinsk fakultet, Molekylärbiologi (Medicinska fakulteten). (Fällman)
Umeå universitet, Medicinsk fakultet, Molekylärbiologi (Medicinska fakulteten). (Fällman)
2005 (engelsk)Inngår i: FEBS Letters, ISSN 0014-5793, E-ISSN 1873-3468, Vol. 579, nr 11, s. 2339-2347Artikkel i tidsskrift (Fagfellevurdert) Published
Abstract [en]

The immune cell specific protein Fyn-T binding protein (Fyb) has been identified as a target of the Yersinia antiphagocytic effector Yersinia outer protein H (YopH), but its role in macrophages is unknown. By using Fyb domains as bait to screen a mouse lymphoma cDNA library, we identified a novel interaction partner, mammalian actin binding protein 1 (mAbp1). We show that mAbp1 binds the Fyb N-terminal via its C-terminally located src homology 3 domain. The interaction between Fyb and mAbp1 is detected in macrophage lysates and the proteins co-localize with F-actin in the leading edge. Hence, mAbp1 is likely to constitute a downstream effector of Fyb involved in F-actin dynamics.

sted, utgiver, år, opplag, sider
2005. Vol. 579, nr 11, s. 2339-2347
Emneord [en]
Actins/metabolism, Adaptor Proteins; Signal Transducing/chemistry/genetics/*metabolism, Amino Acid Motifs, Animals, Bacterial Outer Membrane Proteins/metabolism, Cell Line, Mice, Microfilament Proteins/genetics/*metabolism, Phosphorylation, Phosphotyrosine/metabolism, Protein Binding, Protein Transport, Protein-Tyrosine-Phosphatase/metabolism, Proto-Oncogene Proteins/metabolism, Proto-Oncogene Proteins c-fyn, Two-Hybrid System Techniques, src Homology Domains/genetics, src-Family Kinases/metabolism
Identifikatorer
URN: urn:nbn:se:umu:diva-16652DOI: 10.1016/j.febslet.2005.03.031PubMedID: 15848169OAI: oai:DiVA.org:umu-16652DiVA, id: diva2:156325
Tilgjengelig fra: 2007-10-08 Laget: 2007-10-08 Sist oppdatert: 2018-06-09bibliografisk kontrollert
Inngår i avhandling
1. Antiphagocytosis by Yersinia pseudotuberculosis: role of the YopH target proteins
Åpne denne publikasjonen i ny fane eller vindu >>Antiphagocytosis by Yersinia pseudotuberculosis: role of the YopH target proteins
2006 (engelsk)Doktoravhandling, med artikler (Annet vitenskapelig)
Abstract [en]

The enteropathogenic bacterium Yersinia pseudotuberculosis binds to β1 integrins on a host cell via its surface protein invasin. This event stimulates signal transduction to the actin cytoskeleton of the eukaryotic cell, which allows the cell to engulf the bacterium that is attached to its surface. However, the pathogen Y. pseudotuberculosis can evade such phagocytosis by injecting virulence effectors that interfere with the antipathogenic machinery of the host cells. One of these virulence effectors is the tyrosine phosphatase YopH. Through its enzymatic activity, YopH blocks phagocytosis by affecting the signalling that is associated with cytoskeletal rearrangements.

Cas is a substrate of YopH in both professional and non-professional phagocytes. We showed that YopH binds to the central substrate domain of Cas and that this interaction is required for YopH to target focal adhesion structures in host cells. We also demonstrated that YopH binds another substrate, FAK, through Cas. Moreover, we suggested that targeting of Cas is necessary for the cytotoxic effects mediated by YopH.

The protein Fyb is specific to immune cells, and it has been identified as a substrate of YopH in macrophages. We discovered that both the N-terminal substrate-binding domain and the C-terminal catalytic region of YopH bind Fyb in a phosphotyrosine-dependent manner. Moreover, we observed that both the substrate-binding domain and the phosphatase activity of YopH are essential for the effects of this protein on macrophages, which include dephosphorylation of Fyb, blocking of phagocytosis, and cytotoxicity.

The role of Fyb in macrophages is largely unknown, although there is evidence that this protein is involved in integrin-linked actin organization. We identified a novel interaction partner of Fyb, mAbp1, which is a protein that binds to F-actin. Studies in vitro indicated that mAbp1 binds to the N terminus of Fyb via a C-terminal SH3 domain. We also found that both Fyb and mAbp1 co-localize with F-actin at the leading edges of macrophages. Further studies suggested that mAbp1 influences the spreading of macrophages and the antiphagocytosis mediated by pathogenic Yersinia. These results support a role for Fyb in signalling that affects F-actin dynamics, and they also provide additional insight into the mechanisms involved. Fyb has been shown to form a complex with SKAP-HOM, another substrate of YopH in macrophages. Our data implied that the level of SKAP-HOM protein depends on the presence of Fyb, but the function of the Fyb/SKAP-HOM complex in macrophages has not been determined. However, since Fyb is the only known haematopoietic-specific substrate of YopH, it is possible that Fyb is involved in other antimicrobial functions.

sted, utgiver, år, opplag, sider
Umeå: Molekylärbiologi, 2006. s. 65
Serie
Doctoral thesis / Umeå University, Department of Molecular Biology ; 1072
Emneord
Molecular biology, Cas, Fyb, mAbp1, SKAP-HOM, Yersinia pseudotuberculosis, YopH, Molekylärbiologi
HSV kategori
Forskningsprogram
molekylärbiologi
Identifikatorer
urn:nbn:se:umu:diva-957 (URN)91-7264-219-X (ISBN)
Disputas
2007-02-01, Major Groove, NUS, 6L, Department of Molecular Biology, Umea University, Umea, 09:00 (engelsk)
Opponent
Veileder
Tilgjengelig fra: 2006-12-21 Laget: 2006-12-21 Sist oppdatert: 2019-01-21bibliografisk kontrollert

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