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Glomerular overexpression and increased tyrosine phosphorylation of focal adhesion kinase p125 FAK in lupus‐prone MRL/MP‐lpr/lpr mice
Author(s) -
Noritsugu Morino,
Tarô Matsumoto,
Kazue Ueki,
Toshihide Mimura,
Ken Hamasaki,
Hiroko Kanda,
Takuji Naruse,
Yoshio Yazaki,
Yoshihisa Nojima
Publication year - 1999
Publication title -
immunology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.297
H-Index - 133
eISSN - 1365-2567
pISSN - 0019-2805
DOI - 10.1046/j.1365-2567.1999.00819.x
Subject(s) - focal adhesion , tyrosine kinase , lupus nephritis , kinase , biology , phosphorylation , microbiology and biotechnology , signal transducing adaptor protein , tyrosine phosphorylation , signal transduction , tyrosine , integrin , cancer research , downregulation and upregulation , ptk2 , nephritis , immunology , protein kinase a , medicine , cell , biochemistry , mitogen activated protein kinase kinase , disease , gene
Much progress has been made in understanding how mammalian cells receive a diverse array of external stimuli and convert them into intracellular biochemical signals. Such efforts have identified a large number of signalling molecules. However, our knowledge is limited as to their pathophysiological role in particular diseases. We demonstrate herein that an integrin‐linked signalling molecule, focal adhesion kinase p125 FAK (FAK), is overexpressed in glomeruli of lupus‐prone MRL/MP‐lpr/lpr (MRL‐lpr) mouse as compared to its congeneic MRL‐+/+ strain. Increased expression was specifically demonstrated in glomeruli but not in other tissues examined. The overexpression was observed in 16‐week‐old MRL‐lpr mice with active nephritis, as well as in younger animals at 4 weeks of age. Thus, the upregulation of FAK clearly preceded the clinical onset of nephritis. FAK in MRL‐lpr glomeruli is highly tyrosine phosphorylated and is associated with adapter protein Grb2. Previous in vitro studies have shown that the association of FAK/Grb2 links cell adhesion to the Ras pathway, which ultimately stimulates mitogen‐activated protein (MAP) kinase, an important regulator of cell proliferation. In accordance, we observed constitutive MAP kinase activation in MRL‐lpr glomeruli. Our findings suggest that signalling pathways involving FAK are activated in MRL‐lpr glomeruli, and are likely to play a role in the development and progression of autoimmune‐mediated murine nephritis.