Key points are not available for this paper at this time.
Focal adhesion kinase (FAK) is a protein-tyrosine kinase that associates with multiple cell surface receptors and signaling proteins through which it can modulate the activity of several intracellular signaling pathways. FAK activity can influence the formation of distinct actin cytoskeletal structures such as lamellipodia and stress fibers in part through effects on small Rho GTPases, although the molecular interconnections of these events are not well defined. Here, we report that FAK interacts with p190RhoGEF, a RhoA-specific GDP/GTP exchange factor, in neuronal cells and in brain tissue extracts by co-immunoprecipitation and co-localization analyses. Using a two-hybrid assay and deletion mutagenesis, the binding site of the FAK C-terminal focal adhesion targeting (FAT) the C-terminal of of a binding p190RhoGEF, FAK by a that the of the FAK cell binding FAK and and of a of FAK and of FAK in cells and these events by of cells FAK and of the that FAK with as a signaling of and receptors Rho Focal adhesion kinase (FAK) is a protein-tyrosine kinase that associates with multiple cell surface receptors and signaling proteins through which it can modulate the activity of several intracellular signaling pathways. FAK activity can influence the formation of distinct actin cytoskeletal structures such as lamellipodia and stress fibers in part through effects on small Rho GTPases, although the molecular interconnections of these events are not well defined. Here, we report that FAK interacts with p190RhoGEF, a RhoA-specific GDP/GTP exchange factor, in neuronal cells and in brain tissue extracts by co-immunoprecipitation and co-localization analyses. Using a two-hybrid assay and deletion mutagenesis, the binding site of the FAK C-terminal focal adhesion targeting (FAT) the C-terminal of of a binding p190RhoGEF, FAK by a that the of the FAK cell binding FAK and and of a of FAK and of FAK in cells and these events by of cells FAK and of the that FAK with as a signaling of and receptors Rho Rho are of the that in a of actin cell and cell in and Rho as molecular in of proteins with Rho exchange exchange focal adhesion focal adhesion Rho binding exchange focal adhesion focal adhesion Rho binding the exchange proteins of the of and of Rho can by a of that are the of Rho in the of a in exchange and a of that are in can through the of through as a of that proteins can by protein-tyrosine such as FAK associates with and receptors modulate signaling cell cell and cell and FAK with the formation of actin stress fibers stress formation is of Rho activity in cell FAK activity in the activity of Rho of cells by the of and it is not these events by with that the can the of FAK through a binding the binding of kinase activity and FAK the C-terminal kinase these by and it is of a FAK signaling we FAK as and binding p190RhoGEF, a RhoA-specific the several a and a C-terminal with a that a in the of and proteins the binding of in a the of these binding the in of exchange activity Here, we that FAK of cells FAK with is with the of by and FAK activity of the FAK C-terminal signaling a in FAK Rho and and C-terminal FAK and as and the of a and and the and by and and FAK and and and the with the in on and and and and cells and cells in the the the of of p190RhoGEF, and of the as by and by the a and the of the by with with and and by and in cell and by and brain extracts the and with p190RhoGEF, with in by in and with cells with and in the cells of which FAK and the of the and FAK with FAK p190RhoGEF, as of Rho cells and in with cells in and by and of of with of with and by in and of by of and the of in the as by of cell is as with the of in cells with by of and cells on in on and with in cells with by with cells by of FAK as a the of p190RhoGEF, in the C-terminal of as in a two-hybrid of a with the C-terminal of the of with the and on and a through binding a in and the C-terminal of FAK on and a C-terminal in cells with not of and FAK and and and in a of and FAK in interacts with FAK in co-immunoprecipitation with cells with with FAK that the C-terminal of in the of of FAK with not FAK and with in cells with the and cell of cells with with and with and and the a as in of cells in of and with FAK in neuronal cells and in brain cells with the and cell by and and with assay with of cells with FAK assay and brain tissue is with the of FAK in the by assay cells and brain tissue FAK with the of in the and FAK FAK and in of neuronal cells and in brain extracts and with FAK in cells and with FAK in brain extracts with the binding of FAK and in of brain and and FAK binding is in brain is that as a is brain these the of these proteins in neuronal cell and brain and the of with of and the intracellular of these cells with a FAK and the of in the with and as well as in and of the with the FAK a not of and FAK in the of and in and FAK a and in the with the these the signaling FAK and in of and FAK in the of and FAK in of and of co-localization and with the and in and by of with not and of FAK on in the two-hybrid the C-terminal of interacts with the C-terminal of that the of FAK through by in that is by the that a and the of in FAK by in and with FAK in cells with FAK and that of is not FAK binding of and the of the FAK are cells with the with FAK and and deletion of the not binding FAK of and of two-hybrid assay and the deletion with of of and the in with cells with and deletion of with FAK of in cell is cells with and with a the and the FAK binding in a of and the and with a two-hybrid assay of in and activity C-terminal not the two-hybrid the of in with FAK in deletion of with FAK of cells deletion of in not FAK of in the of a that not with FAK the deletion of binding FAK the that are the binding of the the FAK that the C-terminal of FAK that with the focal adhesion targeting (FAT) of FAK and that a that a binding the FAK not the of which the FAK a the of the the is it in the of targeting of focal is binding p190RhoGEF, cells with and with in cells with not with and in cells the that FAK is the that the the FAK and is in and by neuronal such as can and and such as can FAK cell adhesion FAK binding p190RhoGEF, of cells and the cells in the cells with FAK that the binding cell by FAK and of signaling cells in cell with FAK and FAK cells with of cell cells as FAK by by cells with and cell cells as by by cells with and of cell by in by Rho is in cell activity is as a with cells in are of cell of and of and cell FAK is in and FAK activity is cells are in FAK is in it cells are in and FAK cells are of cells with FAK is in cells and FAK is by of is with the of FAK by as a and of FAK activity a of signaling cells by of in and not in cell by and of cells with FAK and by of with and these events in binding and cells in cells of by with a the of in in assay of binding in a in binding with cells of Rho of not Rho not cell binding and not FAK not as a of FAK activity a FAK in the of the that not binding FAK with and signaling Rho and FAK activity in cells with FAK in with FAK and by of of of the of the of FAK modulate the of in in cells and cells with with the of the cells and by by cells with of the and by in by Rho is in cell activity is as a with cells with are with cells with as a of in cells of in cells of with and of with the of Rho with of and signaling by of with and FAK these that FAK not of p190RhoGEF, that FAK the activity of and Rho of signaling events of FAK and activity can by neuronal can FAK and can signaling and Rho kinase FAK with a FAK in Rho with p190RhoGEF, and in cells with of in cells not a in in cells FAK and Rho through cells with the and FAK and by by cells with of the by and by in by Rho is in cell activity is as a with cells with are of FAK in with of and in and with of with FAK activity with cells and of Rho with and FAK the of FAK activity in through by the of that the in of FAK and the that FAK with as a signaling of and receptors Rho of a FAK and on the multiple that can Rho activity in in the FAK can binding factor, cell surface FAK signaling Rho as well as Rho the that distinct and with FAK can the of FAK signaling Rho FAK as a and of FAK signaling in Rho cell surface and can FAK distinct binding of FAK can the signaling Rho binding of FAK can in binding of FAK can Rho FAK and signaling through and can Rho activity binding of the FAK C-terminal in can Rho is that the binding of FAK influence FAK Rho FAK with actin stress formation of Rho activity in cells FAK signaling and Rho activity the of cells of actin stress fibers and focal in cell that in that FAK is focal and of cells are in part the of FAK and Rho activity actin and focal FAK and in Rho Rho with and of FAK signaling Rho cell is by the that of Rho such as Rho kinase and kinase can the and of cells that signaling such as and and signaling can Rho it is that FAK can Rho through signaling and as FAK binding molecular Rho as a of signaling in Here, we as binding of that that in are with the of and that FAK FAK and p190RhoGEF, it is that these binding modulate the that of is in exchange are the and these in that FAK and are in and in and brain FAK and cells in the of and in that FAK is that FAK and in on and that FAK is in the of by and and are by the of actin which in are by Rho a of FAK in the of these that of signaling of on and that of is with that signaling in the of Rho which is and in of is the of as the in and that FAK through by the FAK the molecular FAK and that the of in surface on of the that it the of the C-terminal that binding the FAK the of the which is the of the FAK a and deletion of not binding deletion of with FAK as by two-hybrid and with the that the the FAK and is in the of the FAK the surface of the FAK binding FAK we FAK and FAK a with p190RhoGEF, FAK and these events are with the of by a of proteins that with are as a of FAK and a molecular of FAK signaling can Rho Rho are of the that in a of actin cell and cell in and Rho as molecular in of proteins with Rho exchange exchange focal adhesion focal adhesion Rho binding exchange focal adhesion focal adhesion Rho binding the exchange proteins of the of and of Rho can by a of that are the of Rho in the of a in exchange and a of that are in can through the of through as a of that proteins can by protein-tyrosine such as FAK FAK associates with and receptors modulate signaling cell cell and cell and FAK with the formation of actin stress fibers stress formation is of Rho activity in cell FAK activity in the activity of Rho of cells by the of and it is not these events by with that the can the of FAK through a binding the binding of kinase activity and FAK the C-terminal kinase these by and it is of a FAK signaling we FAK as and binding p190RhoGEF, a RhoA-specific the several a and a C-terminal with a that a in the of and proteins the binding of in a the of these binding the in of exchange activity Here, we that FAK of cells FAK with is with the of by and FAK activity of the FAK C-terminal signaling a in FAK Rho and and C-terminal FAK and as and the of a and and the and by and and FAK and and and the with the in on and and and and cells and cells in the the the of of p190RhoGEF, and of the as by and by the a and the of the by with with and and by and in cell and by and brain extracts the and with p190RhoGEF, with in by in and with cells with and in the cells of which FAK and the of the and FAK with FAK p190RhoGEF, as of Rho cells and in with cells in and by and of of with of with and by in and of by of and the of in the as by of cell is as with the of in cells with by of and cells on in on and with in cells with by with cells by and and C-terminal FAK and as and the of a and and the and by and and FAK and and and the with the in on and and and and cells and cells in the the the of of p190RhoGEF, and of the as by and by the a and the of the by with with and and by and in cell and by and brain extracts the and with p190RhoGEF, with in by in and with cells with and in the cells of which FAK and the of the and FAK with FAK p190RhoGEF, as of Rho cells and in with Rho cells in and by and of of with of with and by in and of by of and the of in the as by of cell is as with the of in cells with by of and cells on in on and with in cells with by with cells by of FAK as a the of p190RhoGEF, in the C-terminal of as in a two-hybrid of a with the C-terminal of the of with the and on and a through binding a in and the C-terminal of FAK on and a C-terminal in cells with not of and FAK and and and in a of and FAK in interacts with FAK in co-immunoprecipitation with cells with with FAK that the C-terminal of in the of of FAK with not FAK and with in cells with the and cell of cells with with and with and and the a as in of cells in and FAK FAK and in of neuronal cells and in brain extracts and with FAK in cells and with FAK in brain extracts with the binding of FAK and in of brain and and FAK binding is in brain is that as a is brain these the of these proteins in neuronal cell and brain and the of with of and the intracellular of these cells with a FAK and the of in the with and as well as in and of the with the FAK a not of and FAK in the of and in and FAK a and in the with the these the signaling FAK and in of and FAK in the of and FAK in of and of co-localization and with the and in and by of with not and of FAK on in the two-hybrid the C-terminal of interacts with the C-terminal of that the of FAK through by in that is by the that a and the of in FAK by in and with FAK in cells with FAK and that of is not FAK binding of and the of the FAK are cells with the with FAK and and deletion of the not binding FAK of and of two-hybrid assay and the deletion with of of and the in with cells with and deletion of with FAK of in cell is cells with and with a the and the FAK binding in a of and the and with a two-hybrid assay of in and activity C-terminal not the two-hybrid the of in with FAK in deletion of with FAK of cells deletion of in not FAK of in the of a that not with FAK the deletion of binding FAK the that are the binding of the the FAK that the C-terminal of FAK that with the focal adhesion targeting (FAT) of FAK and that a that a binding the FAK not the of which the FAK a the of the the is it in the of targeting of focal is binding p190RhoGEF, cells with and with in cells with not with and in cells the that FAK is the that the the FAK and is in and by neuronal such as can and and such as can FAK cell adhesion FAK binding p190RhoGEF, of cells and the cells in the cells with FAK that the binding cell by FAK and of signaling cells in cell with FAK and FAK cells with of cell cells as FAK by by cells with and cell cells as by by cells with and of cell by in by Rho is in cell activity is as a with cells in are of cell of and of and cell FAK is in and FAK activity is cells are in FAK is in it cells are in and FAK cells are of cells with FAK is in cells and FAK is by of is with the of FAK by as a and of FAK activity a of signaling cells by of in and not in cell by and of cells with FAK and by of with and these events in binding and cells in cells of by with a the of in in assay of binding in a in binding with cells of Rho of not Rho not cell binding and not FAK not as a of FAK activity a FAK in the of the that not binding FAK with and signaling Rho and FAK activity in cells with FAK in with FAK and by of of of the of the of FAK modulate the of in in cells and cells with with the of the cells and by by cells with of the and by in by Rho is in cell activity is as a with cells with are with cells with as a of in cells of in cells of with and of with the of Rho with of and signaling by of with and FAK these that FAK not of p190RhoGEF, that FAK the activity of and Rho of signaling events of FAK and activity can by neuronal can FAK and can signaling and Rho kinase FAK with a FAK in Rho with p190RhoGEF, and in cells with of in cells not a in in cells FAK and Rho through cells with the and FAK and by by cells with of the by and by in by Rho is in cell activity is as a with cells with are of FAK in with of and in and with of with FAK activity with cells and of Rho with and FAK the of FAK activity in through by the of that the in of FAK and the that FAK with as a signaling of and receptors Rho of FAK as a the of p190RhoGEF, in the C-terminal of as in a two-hybrid of a with the C-terminal of the of with the and on and a through binding a in and the C-terminal of FAK on and a C-terminal in cells with not of and FAK in interacts with FAK in co-immunoprecipitation with cells with with FAK that the C-terminal of in the of of FAK with not FAK and with in cells with the and cell of cells with with and with and and the a as in of cells in and FAK FAK and in of neuronal cells and in brain extracts and with FAK in cells and with FAK in brain extracts with the binding of FAK and in of brain and and FAK binding is in brain is that as a is brain these the of these proteins in neuronal cell and brain and the of with of and the intracellular of these cells with a FAK and the of in the with and as well as in and of the with the FAK a not of and FAK in the of and in and FAK a and in the with the these the signaling FAK and in of FAK on in the two-hybrid the C-terminal of interacts with the C-terminal of that the of FAK through by in that is by the that a and the of in FAK by in and with FAK in cells with FAK and that of is not FAK binding the FAK binding in a of and the and with a two-hybrid assay of in and activity C-terminal not the two-hybrid the of in with FAK in deletion of with FAK of cells deletion of in not FAK of in the of a that not with FAK the deletion of binding FAK the that are the binding of the the FAK that the C-terminal of FAK that with the focal adhesion targeting (FAT) of FAK and that a that a binding the FAK not the of which the FAK a the of the the is it in the of targeting of focal is binding p190RhoGEF, cells with and with in cells with not with and in cells the that FAK is the that the the FAK and is in and by neuronal such as can and and such as can FAK cell adhesion FAK binding p190RhoGEF, of cells and the cells in the cells with FAK that the binding cell by cell FAK is in and FAK activity is cells are in FAK is in it cells are in and FAK cells are of cells with FAK is in cells and FAK is by of is with the of FAK by as a and of FAK activity a of signaling cells by of in and not in cell by and of cells with FAK and by of with and these events in binding and cells in cells of by with a the of in in assay of binding in a in binding with cells of Rho of not Rho not cell binding and not FAK not as a of FAK activity a FAK in the of the that not binding FAK with and signaling Rho FAK and FAK activity in cells with FAK in with FAK and by of of of the of the of FAK modulate the of in in cells with cells with as a of in cells of in cells of with and of with the of Rho with of and signaling by of with and FAK these that FAK not of p190RhoGEF, that FAK the activity of FAK and Rho of signaling events of FAK and activity can by neuronal can FAK and can signaling and Rho kinase FAK with a FAK in Rho with p190RhoGEF, and in cells with of in cells not a in in cells of FAK in with of and in and with of with FAK activity with cells and of Rho with and FAK the of FAK activity in through by the of that the in of FAK and the that FAK with as a signaling of and receptors Rho of a FAK and on the multiple that can Rho activity in in the FAK can binding factor, cell surface FAK signaling Rho as well as Rho the that distinct and with FAK can the of FAK signaling Rho FAK as a and FAK with actin stress formation of Rho activity in cells FAK signaling and Rho activity the of cells of actin stress fibers and focal in cell that in that FAK is focal and of cells are in part the of FAK and Rho activity actin and focal FAK and in Rho Rho with and of FAK signaling Rho cell is by the that of Rho such as Rho kinase and kinase can the and of cells that signaling such as and and signaling can Rho it is that FAK can Rho through signaling and as FAK binding molecular Rho as a of signaling in Here, we as binding of that that in are with the of and that FAK FAK and p190RhoGEF, it is that these binding modulate the that of is in exchange are the and these in that FAK and are in and in and brain FAK and cells in the of and in that FAK is that FAK and in on and that FAK is in the of by and and are by the of actin which in are by Rho a of FAK in the of these that of signaling of on and that of is with that signaling in the of Rho which is and in of is the of as the in and that FAK through by the FAK the molecular FAK and that the of in surface on of the that it the of the C-terminal that binding the FAK the of the which is the of the FAK a and deletion of not binding deletion of with FAK as by two-hybrid and with the that the the FAK and is in the of the FAK the surface of the FAK binding FAK we FAK and FAK a with p190RhoGEF, FAK and these events are with the of by a of proteins that with are as a of FAK and a molecular of FAK signaling can Rho of a FAK and on the multiple that can Rho activity in in the FAK can binding factor, cell surface FAK signaling Rho as well as Rho the that distinct and with FAK can the of FAK signaling Rho FAK as a and FAK with actin stress formation of Rho activity in cells FAK signaling and Rho activity the of cells of actin stress fibers and focal in cell that in that FAK is focal and of cells are in part the of FAK and Rho activity actin and focal FAK and in Rho Rho with and of FAK signaling Rho cell is by the that of Rho such as Rho kinase and kinase can the and of cells that signaling such as and and signaling can Rho it is that FAK can Rho through signaling and as FAK binding molecular Rho as a of signaling in Here, we as binding of that that in are with the of and that FAK FAK and p190RhoGEF, it is that these binding modulate the that of is in exchange are the and these in that FAK and are in and in and brain FAK and cells in the of and in that FAK is that FAK and in on and that FAK is in the of by and and are by the of actin which in are by Rho a of FAK in the of these that of signaling of on and that of is with that signaling in the of Rho which is and in of is the of as the in and that FAK through by the FAK the molecular FAK and that the of in surface on of the that it the of the C-terminal that binding the FAK the of the which is the of the FAK a and deletion of not binding deletion of with FAK as by two-hybrid and with the that the the FAK and is in the of the FAK the surface of the FAK binding FAK we FAK and FAK a with p190RhoGEF, FAK and these events are with the of by a of proteins that with are as a of FAK and a molecular of FAK signaling can Rho a of the
Zhai et al. (Sun,) studied this question.
Synapse has enriched 5 closely related papers on similar clinical questions. Consider them for comparative context: