Manipulation of Receptor tyrosine kinase signaling by Neisseria meningitidis
In eukaryotic cells, protein kinases play an important role in transducing extracellular signals, which can be classified on the basis of distinct substrate preferences as serine/threonine kinases and tyrosine kinases. In this project we identify and characterize the role of non-receptor tyrosine kinases (RTKs) involved in uptake of N. meningitidis.
We have determined that the Src protein tyrosine kinases (PTKs) are activated in response to contact with N. meningitidis. We currently analysed the role of the focal adhesion kinase (FAK), which functions in concert with Src in response to ligand-induced integrin clustering and investigated the EGFR-mediated cell signalling events in response to bacterial adhesion.
In a new collaboration with Prof. K. Doran from the San Diego State University, we aim to focus on the characterisation of further non-RTKs, RTKs and key signalling nodes (e.g. Akt, Erk) involved in the adherence and invasion process of N. meningitidis and Streptococcus agalactiae into brain derived endothelial cells, which is a common interest for both groups. This project currently receives funding from BaCaTec .
New funding - 2014-2015
Role of non-receptor tyrosine kinases and activated signaling pathways in bacterial adherence and invasion of host cells (BaCaTec (Bavaria California Technology Center), Förderprojekt Nr. 12 [2013-2])
Slanina H, Mündlein S, Hebling S, Schubert-Unkmeir A. Role of epidermal growth factor receptor signaling in the interaction of Neisseria meningitidis with endothelial cells. Infect Immun. 2013 Dec 30. [Epub ahead of print]
Slanina H, Hebling S, Hauck CR, Schubert-Unkmeir A. Cell Invasion by Neisseria meningitidis Requires a Functional Interplay between the Focal Adhesion Kinase, Src and Cortactin. PLoS One. 7:e39613. 2012.
Slanina H, König A, Hebling S, Hauck CR, Frosch M, Schubert-Unkmeir A. Entry of N. meningitidis into mammalian cells requires Src family Protein-tyrosine kinases. Infect Immun. May;78(5):1905-14 , 2010.