Elk-1 associates with FAK, regulates the expression of FAK and MAP kinases as well as apoptosis in HK-2 cells.
Focal adhesion kinase (FAK), MAP kinases and the nuclear transcription factor Elk-1 have been reported to be implicated in the same cellular processes, however, their direct or indirect interaction and potential function(s) has not been documented. Here, we explored the association of FAK with Elk-1, the implication of Elk-1 in the regulation of FAK and MAP kinases expression as well as apoptosis, in HK-2 cells. Biochemical and immunofluorescence approaches strongly support the association of low molecular weight protein bands, recognized by FAK antibodies, with Elk-1 or p(ser383)Elk-1. The FAK/Elk-1 complex is found, mainly, in the cytoplasm, near the nuclear membrane periphery, raising the possibility that Elk-1 may have alternative extranuclear function(s) in HK-2 cells. Furthermore, we demonstrated that Elk-1 siRNA-mediated knockdown experiments, increased apoptosis. By contrast, Elk-1 siRNA decreased significantly the expression of FAK and MAP kinases, supporting the hypothesis that Elk-1 may act as a potential physiological substrate and regulator of FAK and MAP kinases expression. These results strongly support that Elk-1 protein is a novel binding-protein partner for FAK, a finding that significantly broadens the potential functioning of FAK and Elk-1.
Mamali
Irene
I
Department of Biology, University of Patras, Patras, Greece.
Kotsantis
Panagiotis
P
Lampropoulou
Maria
M
Marmaras
Vassilis J
VJ
D000818:Animals; D017209:Apoptosis / Q000502:physiology*; D002460:Cell Line; D004789:Enzyme Activation; D051416:Focal Adhesion Protein-Tyrosine Kinases / Q000235:genetics / Q000378:metabolism*; D005786:Gene Expression Regulation; D005947:Glucose / Q000378:metabolism; D006801:Humans; D020928:Mitogen-Activated Protein Kinases / Q000235:genetics / Q000378:metabolism*; D010766:Phosphorylation; D011485:Protein Binding; D034741:RNA, Small Interfering / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction / Q000502:physiology; D050807:ets-Domain Protein Elk-1 / Q000235:genetics / Q000378:metabolism*
D034741:RNA, Small Interfering; D050807:ets-Domain Protein Elk-1; D051416:Focal Adhesion Protein-Tyrosine Kinases; D020928:Mitogen-Activated Protein Kinases; D005947:Glucose