The Abl-related Gene Tyrosine Kinase Acts through p190RhoGAP to Inhibit Actomyosin Contractility and Regulate Focal Adhesion Dynamics upon Adhesion to Fibronectin

Molecular Biology of the Cell - Tập 18 Số 10 - Trang 3860-3872 - 2007
Justin G. Peacock1, Ann L. Miller2, William D. Bradley2, Olga Rodriguez3, Donna J. Webb4, Anthony J. Koleske2,5,6
1Department of Molecular Biophysics and Biochemistry, Department of Neurobiology, and Interdepartmental Neuroscience Program, Yale University, New Haven, CT 06511, USA.
2Department of Molecular Biophysics and Biochemistry
3*Department of Cell Biology, The Scripps Research Institute, La Jolla, CA 92037; and
4*Department of Biological Sciences, Vanderbilt University, Nashville, TN 37235
5Department of Neurobiology and
6Interdepartmental Neuroscience Program, Yale University, New Haven, CT 06511;

Tóm tắt

In migrating cells, actin polymerization promotes protrusion of the leading edge, whereas actomyosin contractility powers net cell body translocation. Although they promote F-actin–dependent protrusions of the cell periphery upon adhesion to fibronectin (FN), Abl family kinases inhibit cell migration on FN. We provide evidence here that the Abl-related gene (Arg/Abl2) kinase inhibits fibroblast migration by attenuating actomyosin contractility and regulating focal adhesion dynamics. arg−/− fibroblasts migrate at faster average speeds than wild-type (wt) cells, whereas Arg re-expression in these cells slows migration. Surprisingly, the faster migrating arg−/− fibroblasts have more prominent F-actin stress fibers and focal adhesions and exhibit increased actomyosin contractility relative to wt cells. Interestingly, Arg requires distinct functional domains to inhibit focal adhesions and actomyosin contractility. The kinase domain–containing Arg N-terminal half can act through the RhoA inhibitor p190RhoGAP to attenuate stress fiber formation and cell contractility. However, Arg requires both its kinase activity and its cytoskeleton-binding C-terminal half to fully inhibit focal adhesions. Although focal adhesions do not turn over efficiently in the trailing edge of arg−/− cells, the increased contractility of arg−/− cells tears the adhesions from the substrate, allowing for the faster migration observed in these cells. Together, our data strongly suggest that Arg inhibits cell migration by restricting actomyosin contractility and regulating its coupling to the substrate through focal adhesions.

Từ khóa


Tài liệu tham khảo

Affolter M., 2005, Dev. Cell, 9, 19, 10.1016/j.devcel.2005.06.003

Arora P. D., 1994, J. Cell. Physiol, 159, 161, 10.1002/jcp.1041590120

Bashaw G. J., 2000, Cell, 101, 703, 10.1016/S0092-8674(00)80883-1

Bennett R. L., 1992, Development, 116, 953, 10.1242/dev.116.4.953

10.1091/mbc.e06-02-0132

Chrzanowska-Wodnicka M., 1996, J. Cell Biol, 133, 1403, 10.1083/jcb.133.6.1403

de Rooij J., 2005, J. Cell Biol, 171, 153, 10.1083/jcb.200506152

Frasca F., 2001, Oncogene, 20, 3845, 10.1038/sj.onc.1204531

Grevengoed E. E., 2003, J. Cell Biol, 163, 1267, 10.1083/jcb.200307026

Grevengoed E. E., 2001, J. Cell Biol, 155, 1185, 10.1083/jcb.200105102

Gupton S. L., 2006, Cell, 125, 1361, 10.1016/j.cell.2006.05.029

Hernandez S. E., 2004, Trends Cell Biol, 14, 36, 10.1016/j.tcb.2003.11.003

Hernandez S. E., 2004, Curr. Biol, 14, 691, 10.1016/j.cub.2004.03.062

Jay P. Y., 1995, J. Cell Sci, 108, 387, 10.1242/jcs.108.1.387

Jockusch B. M., 1995, Annu. Rev. Cell Dev. Biol, 11, 379, 10.1146/annurev.cb.11.110195.002115

Kaibuchi K., 1999, Prog. Mol. Subcell. Biol, 22, 23, 10.1007/978-3-642-58591-3_2

Kain K. H., 2001, J. Biol. Chem, 276, 16185, 10.1074/jbc.M100095200

Koleske A. J., 2006, Regulation of Cytoskeletal Dynamics and Cell Morphogenesis by Abl Family Kinases, 10.1007/978-0-387-68744-5_5

Koleske A. J., 1998, Neuron, 21, 1259, 10.1016/S0896-6273(00)80646-7

Kruh G. D., 1990, Proc. Natl. Acad. Sci. USA, 87, 5802, 10.1073/pnas.87.15.5802

Lauffenburger D. A., 1996, Cell, 84, 359, 10.1016/S0092-8674(00)81280-5

Liebl E. C., 2000, Neuron, 26, 107, 10.1016/S0896-6273(00)81142-3

Lin C. H., 1995, Neuron, 14, 763, 10.1016/0896-6273(95)90220-1

Miller A. L., 2004, J. Cell Biol, 165, 407, 10.1083/jcb.200308055

Mitchison T. J., 1996, Cell, 84, 371, 10.1016/S0092-8674(00)81281-7

Moresco E. M., 2005, J. Neurosci, 25, 6105, 10.1523/JNEUROSCI.1432-05.2005

Murphy K. H., 1987, J. Periodont. Res, 22, 342, 10.1111/j.1600-0765.1987.tb01596.x

Nobes C. D., 1995, Cell, 81, 53, 10.1016/0092-8674(95)90370-4

Pendergast A. M., 2002, Adv. Cancer Res, 85, 51, 10.1016/S0065-230X(02)85003-5

Pertz O., 2006, Nature, 440, 1069, 10.1038/nature04665

Plattner R., 2003, Nat. Cell Biol, 5, 309, 10.1038/ncb949

Plattner R., 2004, Mol. Cell. Biol, 24, 2573, 10.1128/MCB.24.6.2573-2583.2004

Pollard T. D., 2003, Cell, 112, 453, 10.1016/S0092-8674(03)00120-X

Ponti A., 2004, Science, 305, 1782, 10.1126/science.1100533

Ridley A. J., 2001, J. Cell Sci, 114, 2713, 10.1242/jcs.114.15.2713

Ridley A. J., 1992, Cell, 70, 389, 10.1016/0092-8674(92)90163-7

Ridley A. J., 2003, Science, 302, 1704, 10.1126/science.1092053

Rottner K., 1999, Curr. Biol, 9, 640, 10.1016/S0960-9822(99)80286-3

Smilenov L. B., 1999, Science, 286, 1172, 10.1126/science.286.5442.1172

Straight A. F., 2003, Science, 299, 1743, 10.1126/science.1081412

Suter D. M., 1998, J. Cell Biol, 141, 227, 10.1083/jcb.141.1.227

Wang B., 1996, Oncogene, 13, 1379

Wang Y., 2001, Proc. Natl. Acad. Sci. USA, 98, 14865, 10.1073/pnas.251249298

Webb D. J., 2002, Nat. Cell Biol, 4, E97, 10.1038/ncb0402-e97

Wills Z., 1999, Neuron, 22, 301, 10.1016/S0896-6273(00)81091-0

Wills Z., 2002, Neuron, 36, 611, 10.1016/S0896-6273(02)01022-X

Wills Z., 1999, Neuron, 22, 291, 10.1016/S0896-6273(00)81090-9

Woodring P. J., 2003, J. Cell Sci, 116, 2613, 10.1242/jcs.00622

Woodring P. J., 2002, J. Cell Biol, 156, 879, 10.1083/jcb.200110014

Woodring P. J., 2004, J. Cell Biol, 165, 493, 10.1083/jcb.200312171

Thông tin
Thông tin xuất bản

Molecular Biology of the Cell

Tập 18 Số 10

3860-3872

Thông tin tác giả