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Regulation of cell motility by mitogen-activated protein kinase.

Klemke RL, Cai S, Giannini AL, Gallagher PJ, de Lanerolle P, Cheresh DA - J. Cell Biol. (1997)

Bottom Line: Inhibition of MAP kinase activity causes decreased MLCK function, MLC phosphorylation, and cell migration on extracellular matrix proteins.In vitro results support these findings since ERK-phosphorylated MLCK has an increased capacity to phosphorylate MLC and shows increased sensitivity to calmodulin.Thus, we define a signaling pathway directly downstream of MAP kinase, influencing cell migration on the extracellular matrix.

View Article: PubMed Central - PubMed

Affiliation: Department of Immunology, The Scripps Research Institute, La Jolla, California 92037, USA.

ABSTRACT
Cell interaction with adhesive proteins or growth factors in the extracellular matrix initiates Ras/mitogen-activated protein (MAP) kinase signaling. Evidence is provided that MAP kinase (ERK1 and ERK2) influences the cells' motility machinery by phosphorylating and, thereby, enhancing myosin light chain kinase (MLCK) activity leading to phosphorylation of myosin light chains (MLC). Inhibition of MAP kinase activity causes decreased MLCK function, MLC phosphorylation, and cell migration on extracellular matrix proteins. In contrast, expression of mutationally active MAP kinase kinase causes activation of MAP kinase leading to phosphorylation of MLCK and MLC and enhanced cell migration. In vitro results support these findings since ERK-phosphorylated MLCK has an increased capacity to phosphorylate MLC and shows increased sensitivity to calmodulin. Thus, we define a signaling pathway directly downstream of MAP kinase, influencing cell migration on the extracellular matrix.

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Model depicting role of MAP kinase in cell migration.  Proposed signaling pathway leading from integrin or growth factor receptor ligation to activation of cell migration. This model  takes into account that MAP kinase can be activated by integrins  and/or growth factors. As shown in this study, once activated,  MAP kinase can phosphorylate MLCK, which in turn shows enhanced activity as measured by its ability to phosphorylate MLC.  This model assumes that this phosphorylated MLC regulates the  cell's actin-myosin motor function, thereby facilitating contraction leading to cell movement on the extracellular matrix.
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Figure 8: Model depicting role of MAP kinase in cell migration. Proposed signaling pathway leading from integrin or growth factor receptor ligation to activation of cell migration. This model takes into account that MAP kinase can be activated by integrins and/or growth factors. As shown in this study, once activated, MAP kinase can phosphorylate MLCK, which in turn shows enhanced activity as measured by its ability to phosphorylate MLC. This model assumes that this phosphorylated MLC regulates the cell's actin-myosin motor function, thereby facilitating contraction leading to cell movement on the extracellular matrix.

Mentions: Based on the experiments described above and the work of others, it is now possible to develop a model that depicts the signaling pathway leading from integrin and/or growth factor ligation to myosin activation and cell migration (Fig. 8). This model identifies a signaling pathway involving the ability of MAP kinase to directly phosphorylate MLCK, which in turn is better able to phosphorylate MLC. Importantly, this pathway is independent of the ability of MAP kinase to translocate to the nucleus where it activates gene transcriptional events involved in cell proliferation and differentiation.


Regulation of cell motility by mitogen-activated protein kinase.

Klemke RL, Cai S, Giannini AL, Gallagher PJ, de Lanerolle P, Cheresh DA - J. Cell Biol. (1997)

Model depicting role of MAP kinase in cell migration.  Proposed signaling pathway leading from integrin or growth factor receptor ligation to activation of cell migration. This model  takes into account that MAP kinase can be activated by integrins  and/or growth factors. As shown in this study, once activated,  MAP kinase can phosphorylate MLCK, which in turn shows enhanced activity as measured by its ability to phosphorylate MLC.  This model assumes that this phosphorylated MLC regulates the  cell's actin-myosin motor function, thereby facilitating contraction leading to cell movement on the extracellular matrix.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC2139771&req=5

Figure 8: Model depicting role of MAP kinase in cell migration. Proposed signaling pathway leading from integrin or growth factor receptor ligation to activation of cell migration. This model takes into account that MAP kinase can be activated by integrins and/or growth factors. As shown in this study, once activated, MAP kinase can phosphorylate MLCK, which in turn shows enhanced activity as measured by its ability to phosphorylate MLC. This model assumes that this phosphorylated MLC regulates the cell's actin-myosin motor function, thereby facilitating contraction leading to cell movement on the extracellular matrix.
Mentions: Based on the experiments described above and the work of others, it is now possible to develop a model that depicts the signaling pathway leading from integrin and/or growth factor ligation to myosin activation and cell migration (Fig. 8). This model identifies a signaling pathway involving the ability of MAP kinase to directly phosphorylate MLCK, which in turn is better able to phosphorylate MLC. Importantly, this pathway is independent of the ability of MAP kinase to translocate to the nucleus where it activates gene transcriptional events involved in cell proliferation and differentiation.

Bottom Line: Inhibition of MAP kinase activity causes decreased MLCK function, MLC phosphorylation, and cell migration on extracellular matrix proteins.In vitro results support these findings since ERK-phosphorylated MLCK has an increased capacity to phosphorylate MLC and shows increased sensitivity to calmodulin.Thus, we define a signaling pathway directly downstream of MAP kinase, influencing cell migration on the extracellular matrix.

View Article: PubMed Central - PubMed

Affiliation: Department of Immunology, The Scripps Research Institute, La Jolla, California 92037, USA.

ABSTRACT
Cell interaction with adhesive proteins or growth factors in the extracellular matrix initiates Ras/mitogen-activated protein (MAP) kinase signaling. Evidence is provided that MAP kinase (ERK1 and ERK2) influences the cells' motility machinery by phosphorylating and, thereby, enhancing myosin light chain kinase (MLCK) activity leading to phosphorylation of myosin light chains (MLC). Inhibition of MAP kinase activity causes decreased MLCK function, MLC phosphorylation, and cell migration on extracellular matrix proteins. In contrast, expression of mutationally active MAP kinase kinase causes activation of MAP kinase leading to phosphorylation of MLCK and MLC and enhanced cell migration. In vitro results support these findings since ERK-phosphorylated MLCK has an increased capacity to phosphorylate MLC and shows increased sensitivity to calmodulin. Thus, we define a signaling pathway directly downstream of MAP kinase, influencing cell migration on the extracellular matrix.

Show MeSH
Related in: MedlinePlus