Open AccessPaxillin phosphorylation: bifurcation point downstream of integrin‐linked kinase (ILK) in streptococcal invasion
Author(s) -
Wang Beinan,
Li Shaoying,
Dedhar Shoukat,
Cleary P. Patrick
Publication year - 2007
Publication title -
cellular microbiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.542
H-Index - 138
eISSN - 1462-5822
pISSN - 1462-5814
DOI - 10.1111/j.1462-5822.2007.00889.x
Subject(s) - paxillin , phosphorylation , biology , microbiology and biotechnology , tyrosine phosphorylation , integrin linked kinase , focal adhesion , integrin , proto oncogene tyrosine protein kinase src , kinase , protein kinase a , biochemistry , receptor , cyclin dependent kinase 2
Summary Efficient group A streptococcus (GAS) invasion of mammalian cells requires fibronectin (Fn) binding proteins, such as M1 and PrtF1/SfbI, that bridge bacteria to integrins and activate cellular signalling for ingestion. Previous studies of GAS invasion, mediated by both proteins, suggest a common signalling pathway. However, distinct cellular morphological changes at the port of bacterial entry suggest that different signals are also induced. Here we report that paxillin is phosphorylated in response to Fn‐bound GAS that express either M1 or PrtF1/SfbI protein, but is not phosphorylated in response to a mutant deficient in both proteins. Inhibition of paxillin phosphorylation by a tyrosine kinase inhibitor, PP2, or by expression of a dominant negative form of paxillin significantly reduced invasion by M1 + but did not affect ingestion of PrtF1/SfbI + strains. In contrast, another tyrosine inhibitor, genistein, did not significantly prevent paxillin phosphorylation and had no effect on ingestion of the M1 + strain, but reduced PrtF1/SfbI‐mediated entry. This suggests that paxillin phosphorylation is induced by both proteins but only required for M1‐mediated invasion. A bifurcation point, downstream of integrin‐linked kinase (ILK) and phosphoinositide 3‐kinase, likely accounts for the distinct morphological changes. Furthermore, ILK activity is indispensable for M1‐induced paxillin recruitment and phosphorylation.