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Focal adhesion kinase is redistributed to focal complexes and mediates cell spreading in macrophages in response to M-CSF.
Biol Chem. 2005 Sep; 386(9):919-29.BC

Abstract

The macrophage colony-stimulating factor (M-CSF, CSF-1) regulates survival, proliferation and differentiation of mononuclear phagocytes, as well as macrophage motility and morphology. The latter features are usually regulated by ECM-mediated activation of integrins and subsequent tyrosine phosphorylation of cellular proteins, including focal adhesion kinase (FAK). FAK is phosphorylated by downstream receptor tyrosine kinases as well. We addressed the question whether M-CSF regulates FAK tyrosine phosphorylation in macrophages, and found that M-CSF induces FAK phosphorylation at all known tyrosine residues. This phosphorylation was dependent on Src. Extracellularly-regulated kinase (ERK), Jun N-terminal kinase (JNK) and phosphatidylinositol-3-kinase (PI3K) were found to be negatively involved in M-CSF-induced FAK phosphorylation, as their inhibition resulted in FAK hyper-phosphorylation. Following M-CSF treatment, FAK and the active forms of M-CSFR and Src were redistributed to the cytoskeleton, where active ERK, JNK and PI3K were detectable. Immunofluorescence showed the presence of FAK and its active form in focal complexes following M-CSF treatment. Moreover, cell spreading and adhesion were impaired when FAK tyrosine phosphorylation was abrogated by either transfection with FRNK, a dominant negative form of FAK, or treatment with a number of inhibitors of upstream FAK-activating signals. These results point to a relevant role for FAK in the regulation of cell spreading and adhesion in macrophages.

Authors+Show Affiliations

Dipartimento di Patologia e Oncologia Sperimentali, Università di Firenze, Viale G.B. Morgagni 50, I-50134 Firenze, Italy.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

16164417

Citation

Rovida, Elisabetta, et al. "Focal Adhesion Kinase Is Redistributed to Focal Complexes and Mediates Cell Spreading in Macrophages in Response to M-CSF." Biological Chemistry, vol. 386, no. 9, 2005, pp. 919-29.
Rovida E, Lugli B, Barbetti V, et al. Focal adhesion kinase is redistributed to focal complexes and mediates cell spreading in macrophages in response to M-CSF. Biol Chem. 2005;386(9):919-29.
Rovida, E., Lugli, B., Barbetti, V., Giuntoli, S., Olivotto, M., & Dello Sbarba, P. (2005). Focal adhesion kinase is redistributed to focal complexes and mediates cell spreading in macrophages in response to M-CSF. Biological Chemistry, 386(9), 919-29.
Rovida E, et al. Focal Adhesion Kinase Is Redistributed to Focal Complexes and Mediates Cell Spreading in Macrophages in Response to M-CSF. Biol Chem. 2005;386(9):919-29. PubMed PMID: 16164417.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Focal adhesion kinase is redistributed to focal complexes and mediates cell spreading in macrophages in response to M-CSF. AU - Rovida,Elisabetta, AU - Lugli,Benedetta, AU - Barbetti,Valentina, AU - Giuntoli,Serena, AU - Olivotto,Massimo, AU - Dello Sbarba,Persio, PY - 2005/9/17/pubmed PY - 2005/12/13/medline PY - 2005/9/17/entrez SP - 919 EP - 29 JF - Biological chemistry JO - Biol Chem VL - 386 IS - 9 N2 - The macrophage colony-stimulating factor (M-CSF, CSF-1) regulates survival, proliferation and differentiation of mononuclear phagocytes, as well as macrophage motility and morphology. The latter features are usually regulated by ECM-mediated activation of integrins and subsequent tyrosine phosphorylation of cellular proteins, including focal adhesion kinase (FAK). FAK is phosphorylated by downstream receptor tyrosine kinases as well. We addressed the question whether M-CSF regulates FAK tyrosine phosphorylation in macrophages, and found that M-CSF induces FAK phosphorylation at all known tyrosine residues. This phosphorylation was dependent on Src. Extracellularly-regulated kinase (ERK), Jun N-terminal kinase (JNK) and phosphatidylinositol-3-kinase (PI3K) were found to be negatively involved in M-CSF-induced FAK phosphorylation, as their inhibition resulted in FAK hyper-phosphorylation. Following M-CSF treatment, FAK and the active forms of M-CSFR and Src were redistributed to the cytoskeleton, where active ERK, JNK and PI3K were detectable. Immunofluorescence showed the presence of FAK and its active form in focal complexes following M-CSF treatment. Moreover, cell spreading and adhesion were impaired when FAK tyrosine phosphorylation was abrogated by either transfection with FRNK, a dominant negative form of FAK, or treatment with a number of inhibitors of upstream FAK-activating signals. These results point to a relevant role for FAK in the regulation of cell spreading and adhesion in macrophages. SN - 1431-6730 UR - https://www.unboundmedicine.com/medline/citation/16164417/Focal_adhesion_kinase_is_redistributed_to_focal_complexes_and_mediates_cell_spreading_in_macrophages_in_response_to_M_CSF_ L2 - https://www.degruyter.com/document/doi/10.1515/BC.2005.107 DB - PRIME DP - Unbound Medicine ER -