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Paxillin and focal adhesion signalling

Nature Cell Biology volume 2, pages E231–E236 (2000)Cite this article

Abstract

To facilitate a rapid response to environmental change, cells use scaffolding — or adaptor — proteins to recruit key components of their signal-transduction machinery to specific subcellular locations. Paxillin is a multi-domain adaptor found at the interface between the plasma membrane and the actin cytoskeleton. Here it provides a platform for the integration and processing of adhesion- and growth factor-related signals.

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Figure 1: Integrin and growth-factor signalling through paxillin, and interactions with the actin cytoskeleton.
Figure 2: The paxillin family and domain structure.

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References

  1. Burridge, K. & Chrzanowska-Wodnicka, M. Focal adhesions, contractility, and signaling. Annu. Rev. Cell Dev. Biol. 12, 463–518 ( 1996).

    Article  CAS  Google Scholar 

  2. Giancotti, F. G. & Ruoslahti, E. Integrin signaling . Science 285, 1028–1032 (1999).

    Article  CAS  Google Scholar 

  3. Schwartz, M. A. & Baron, V. Interactions between mitogenic stimuli, or, a thousand and one connections. Curr. Opin. Cell Biol. 11, 197–202 ( 1999).

    Article  CAS  Google Scholar 

  4. Rozengurt, E. Convergent signalling in the action of integrins, neuropeptides, growth factors and oncogenes. Cancer Surv. 24, 81– 96 (1995).

    CAS  PubMed  Google Scholar 

  5. Miyamoto, S., Teramoto, H., Gutkind, J. S. & Yamada, K. M. Integrins can collaborate with growth factors for phosphorylation of receptor tyrosine kinases and MAP kinase activation: roles of integrin aggregation and occupancy of receptors. J. Cell Biol. 135, 1633–1642 (1996).

    Article  CAS  Google Scholar 

  6. Schwartz, M. A., Schaller, M. D. & Ginsberg, M. H. Integrins: emerging paradigms of signal transduction. Annu. Rev. Cell Dev. Biol. 11, 549–599 (1995).

    Article  CAS  Google Scholar 

  7. Giancotti, F. G. Complexity and specificity of integrin signalling. Nature Cell Biol. 2, E13–E14 ( 2000).

    Article  CAS  Google Scholar 

  8. Turner, C. E. Paxillin. Int. J. Biochem. Cell Biol. 30, 955–959 (1998).

    Article  CAS  Google Scholar 

  9. Mazaki, Y., Hashimoto, S. & Sabe, H. Monocyte cells and cancer cells express novel paxillin isoforms with different binding properties to focal adhesion proteins. J. Biol. Chem. 272, 7437–7444 (1997).

    Article  CAS  Google Scholar 

  10. Brown, M. C., Curtis, M. S. & Turner, C. E. Paxillin LD motifs may define a new family of protein recognition domains. Nature Struct. Biol. 5, 677–678 (1998).

    Article  CAS  Google Scholar 

  11. Thomas, S. M., Hagel, M. & Turner, C. E. Characterization of a focal adhesion protein, Hic-5, that shares extensive homology with paxillin. J. Cell Sci. 112, 181–190 (1999).

    CAS  PubMed  Google Scholar 

  12. Lipsky, B. P., Beals, C. R. & Staunton, D. E. Leupaxin is a novel LIM domain protein that forms a complex with PYK2. J. Biol. Chem. 273, 11709–11713 (1998).

    Article  CAS  Google Scholar 

  13. Yang, L., Guerrero, J., Hong, H., DeFranco, D. B. & Stallcup, M. R. Interaction of the tau2 transcriptional activation domain of glucocorticoid receptor with a novel steroid receptor coactivator, Hic-5, which localizes to both focal adhesions and the nuclear matrix. Mol. Biol. Cell 11, 2007– 2018 (2000).

    Article  CAS  Google Scholar 

  14. Shibanuma, M., Mashimo, J., Kuroki, T. & Nose, K. Characterization of the TGF beta 1-inducible hic-5 gene that encodes a putative novel zinc finger protein and its possible involvement in cellular senescence. J. Biol. Chem. 269, 26767– 26774 (1994).

    CAS  PubMed  Google Scholar 

  15. Akiyama, N., Matsuo, Y., Sai, H., Noda, M. & Kizaka-Kondoh, S. Identification of a series of transforming growth factor beta-responsive genes by retrovirus-mediated gene trap screening . Mol. Cell Biol. 20, 3266– 3273 (2000).

    Article  CAS  Google Scholar 

  16. Sattler, M., Pisick, E., Morrison, P. T. & Salgia, R. Role of the cytoskeletal protein paxillin in oncogenesis. Crit. Rev. Onc. 11, 63–76 ( 2000).

    CAS  Google Scholar 

  17. Pawson, T. & Scott, J. D. Signaling through scaffold, anchoring, and adaptor proteins. Science 278, 2075–2080 (1997).

    Article  CAS  Google Scholar 

  18. Gill, G. N. The enigma of LIM domains. Structure 3, 1285–1289 (1995).

    Article  CAS  Google Scholar 

  19. Brown, M. C., Perrotta, J. A. & Turner, C. E. Identification of LIM3 as the principal determinant of paxillin focal adhesion localization and characterization of a novel motif on paxillin directing vinculin and focal adhesion kinase binding. J. Cell Biol. 135, 1109–1123 (1996).

    Article  CAS  Google Scholar 

  20. Liu, S. et al. Binding of paxillin to alpha4 integrins modifies integrin-dependent biological responses. Nature 402, 676– 681 (1999).

    Article  CAS  Google Scholar 

  21. Lauffenburger, D. A. & Horwitz, A. F. Cell migration: a physically integrated molecular process. Cell 84, 359–369 (1996).

    Article  CAS  Google Scholar 

  22. Angers-Loustau, A. et al. Protein tyrosine phosphatase-PEST regulates focal adhesion disassembly, migration, and cytokinesis in fibroblasts. J. Cell Biol. 144, 1019–1031 ( 1999).

    Article  CAS  Google Scholar 

  23. Shen, Y., Schneider, G., Cloutier, J. F., Veillette, A. & Schaller, M. D. Direct association of protein-tyrosine phosphatase PTP-PEST with paxillin. J. Biol. Chem. 273, 6474–6481 ( 1998).

    Article  CAS  Google Scholar 

  24. Coté, J. F., Turner, C. E. & Tremblay, M. L. Intact LIM 3 and LIM 4 domains of paxillin are required for the association to a novel polyproline region (Pro 2) of protein-tyrosine phosphatase-PEST. J. Biol. Chem. 274 , 20550–20560 (1999).

    Article  Google Scholar 

  25. Davidson, D., Cloutier, J. F., Gregorieff, A. & Veillette, A. Inhibitory tyrosine protein kinase p50csk is associated with protein-tyrosine phosphatase PTP-PEST in hemopoietic and non-hemopoietic cells. J. Biol. Chem. 272, 23455–23462 (1997).

    Article  CAS  Google Scholar 

  26. Sabe, H., Hata, A., Okada, M., Nakagawa, H. & Hanafusa, H. Analysis of the binding of the Src homology 2 domain of Csk to tyrosine-phosphorylated proteins in the suppression and mitotic activation of c-Src. Proc. Natl Acad. Sci. USA 91, 3984–3988 (1994).

    Article  CAS  Google Scholar 

  27. Brown, M. C., Perrotta, J. A. & Turner, C. E. Serine and threonine phosphorylation of the paxillin LIM domains regulates paxillin focal adhesion localization and cell adhesion to fibronectin. Mol. Biol. Cell 9, 1803– 1816 (1998).

    Article  CAS  Google Scholar 

  28. Brown, M. C. & Turner, C. E. Characterization of paxillin LIM domain-associated serine threonine kinases: activation by angiotensin II in vascular smooth muscle cells. J. Cell Biochem. 76, 99–108 ( 1999).

    Article  CAS  Google Scholar 

  29. Herreros, L. et al. Paxillin localizes to the lymphocyte microtubule organizing center and associates with the microtubule cytoskeleton. J. Biol. Chem. 275, 26436–26440 ( 2000).

    Article  CAS  Google Scholar 

  30. Sancho, D. et al. The tyrosine kinase PYK-2/RAFTK regulates natural killer (NK) cell cytotoxic response, and is translocated and activated upon specific target cell recognition and killing. J. Cell Biol. 149, 1249–1262 (2000).

    Article  CAS  Google Scholar 

  31. Waterman-Storer, C. M., Worthylake, R. A., Liu, B. P., Burridge, K. & Salmon, E. D. Microtubule growth activates Rac1 to promote lamellipodial protrusion in fibroblasts. Nature Cell Biol. 1, 45–50 (1999).

    Article  CAS  Google Scholar 

  32. Kaverina, I., Krylyshkina, O. & Small, J. V. Microtubule targeting of substrate contacts promotes their relaxation and dissociation. J. Cell Biol. 146 , 1033–1044 (1999).

    Article  CAS  Google Scholar 

  33. Kaplan, K. B. et al. Association of the amino-terminal half of c-Src with focal adhesions alters their properties and is regulated by phosphorylation of tyrosine 527. EMBO J. 13, 4745–4756 (1994).

    Article  CAS  Google Scholar 

  34. Burridge, K., Turner, C. E. & Romer, L. H. Tyrosine phosphorylation of paxillin and pp125FAK accompanies cell adhesion to extracellular matrix: a role in cytoskeletal assembly. J. Cell Biol. 119, 893– 903 (1992).

    Article  CAS  Google Scholar 

  35. Schaller, M. D. & Parsons, J. T. pp125FAK-dependent tyrosine phosphorylation of paxillin creates a high-affinity binding site for Crk. Mol. Cell. Biol. 15, 2635– 2645 (1995).

    Article  CAS  Google Scholar 

  36. Bellis, S. L., Miller, J. T. & Turner, C. E. Characterization of tyrosine phosphorylation of paxillin in vitro by focal adhesion kinase. J. Biol. Chem. 270, 17437–17441 ( 1995).

    Article  CAS  Google Scholar 

  37. Richardson, A., Malik, R. K., Hildebrand, J. D. & Parsons, J. T. Inhibition of cell spreading by expression of the C-terminal domain of focal adhesion kinase (FAK) is rescued by coexpression of Src or catalytically inactive FAK: a role for paxillin tyrosine phosphorylation. Mol. Cell. Biol. 17, 6906–6914 (1997).

    Article  CAS  Google Scholar 

  38. Feller, S. M.,. et al. Physiological signals and oncogenesis mediated through Crk family adaptor proteins. J. Cell Physiol. 177, 535–552 (1998).

    Article  CAS  Google Scholar 

  39. Petit, V. et al. Phosphorylation of tyrosine residues 31 and 118 on paxillin regulates cell migration through an association with CRK in NBT-II cells. J. Cell Biol. 148, 957–970 (2000).

    Article  CAS  Google Scholar 

  40. Klemke, R. L. et al. CAS/Crk coupling serves as a “molecular switch” for induction of cell migration. J. Cell Biol. 140, 961–972 (1998).

    Article  CAS  Google Scholar 

  41. Escalante, M. et al. Phosphorylation of c-Crk II on the negative regulatory Tyr222 mediates Nerve Growth Factor-induced cell spreading and morphogenesis. J. Biol. Chem. 275, 24787–24797 (2000).

    Article  CAS  Google Scholar 

  42. Shen, Y. et al. The noncatalytic domain of protein-tyrosine phosphatase-PEST targets paxillin for dephosphorylation in vivo. J. Biol. Chem. 275, 1405–1413 ( 2000).

    Article  CAS  Google Scholar 

  43. Howell, B. W. & Cooper, J. A. Csk suppression of Src involves movement of Csk to sites of Src activity. Mol. Cell. Biol. 14, 5402–5411 ( 1994).

    Article  CAS  Google Scholar 

  44. Lewis, J. M., Baskaran, R., Taagepera, S., Schwartz, M. A. & Wang, J. Y. Integrin regulation of c-Abl tyrosine kinase activity and cytoplasmic- nuclear transport. Proc. Natl Acad. Sci. USA 93, 15174– 15179 (1996).

    Article  CAS  Google Scholar 

  45. Bellis, S. L., Perrotta, J. A., Curtis, M. S. & Turner, C. E. Adhesion of fibroblasts to fibronectin stimulates both serine and tyrosine phosphorylation of paxillin. Biochem. J. 325, 375–381 (1997).

    Article  CAS  Google Scholar 

  46. De Nichilo, M. O. & Yamada, K. M. Integrin alpha v beta 5-dependent serine phosphorylation of paxillin in cultured human macrophages adherent to vitronectin. J. Biol. Chem. 271, 11016–11022 (1996).

    Article  CAS  Google Scholar 

  47. Riedy, M. C., Brown, M. C., Molloy, C. J. & Turner, C. E. Activin A and TGF-β stimulate phosphorylation of focal adhesion proteins and cytoskeletal reorganization in rat aortic smooth muscle cells. Exp. Cell Res. 251, 194–202 (1999).

    Article  CAS  Google Scholar 

  48. Yamaguchi, R., Mazaki, Y., Hirota, K., Hashimoto, S. & Sabe, H. Mitosis specific serine phosphorylation and downregulation of one of the focal adhesion protein, paxillin . Oncogene 15, 1753–1761 (1997).

    Article  CAS  Google Scholar 

  49. Daniels, R. H. & Bokoch, G. M. p21-activated protein kinase: a crucial component of morphological signaling? Trends Biochem. Sci. 24, 350–355 (1999).

    Article  CAS  Google Scholar 

  50. Ku, H. & Meier, K. E. Phosphorylation of paxillin via the ERK mitogen-activated protein kinase cascade in EL4 thymoma cells. J. Biol. Chem. 275, 11333–11340 (2000).

    Article  CAS  Google Scholar 

  51. Sastry, S. K. et al. Quantitative changes in integrin and focal adhesion signaling regulate myoblast cell cycle withdrawal. J. Cell Biol. 144, 1295–1309 (1999).

    Article  CAS  Google Scholar 

  52. Wera, S. & Hemmings, B. A. Serine/threonine protein phosphatases. Biochem. J. 311, 17 –29 (1995).

    Article  CAS  Google Scholar 

  53. Ito, A. et al. A truncated isoform of the PP2A B56 subunit promotes cell motility through paxillin phosphorylation. EMBO J. 19, 562–571 (2000).

    Article  CAS  Google Scholar 

  54. Critchley, D. R. Focal adhesions - the cytoskeletal connection. Curr. Opin. Cell Biol. 12, 133–139 ( 2000).

    Article  CAS  Google Scholar 

  55. Hanks, S. K. & Polte, T. R. Signaling through focal adhesion kinase. Bioessays 19, 137 –145 (1997).

    Article  CAS  Google Scholar 

  56. Wood, C. K., Turner, C. E., Jackson, P. & Critchley, D. R. Characterisation of the paxillin-binding site and the C-terminal focal adhesion targeting sequence in vinculin. J. Cell Sci. 107, 709–717 (1994).

    CAS  PubMed  Google Scholar 

  57. Tachibana, K., Sato, T., D'Avirro, N. & Morimoto, C. Direct association of pp125FAK with paxillin, the focal adhesion- targeting mechanism of pp125FAK. J. Exp. Med. 182, 1089–1099 (1995).

    Article  CAS  Google Scholar 

  58. Tong, X. & Howley, P. M. The bovine papillomavirus E6 oncoprotein interacts with paxillin and disrupts the actin cytoskeleton . Proc. Natl Acad. Sci. USA 94, 4412– 4417 (1997).

    Article  CAS  Google Scholar 

  59. Tong, X., Salgia, R., Li, J. L., Griffin, J. D. & Howley, P. M. The bovine papillomavirus E6 protein binds to the LD motif repeats of paxillin and blocks its interaction with vinculin and the focal adhesion kinase. J. Biol. Chem. 272, 33373–33376 (1997).

    Article  CAS  Google Scholar 

  60. Vande Pol, S. B., Brown, M. C. & Turner, C. E. Association of bovine papillomavirus type 1 E6 oncoprotein with the focal adhesion protein paxillin through a conserved protein interaction motif. Oncogene 16, 43–52 (1998).

    Article  CAS  Google Scholar 

  61. Nikolopoulos, S. N. & Turner, C. E. Actopaxin: a new focal- adhesion protein that binds paxillin LD motifs and actin and regulates cell adhesion. J. Cell Biol. (in the press).

  62. Turner, C. E. et al. Paxillin LD4 motif binds PAK and PIX through a novel 95-kD ankyrin repeat, ARF-GAP protein: A role in cytoskeletal remodeling. J. Cell Biol. 145, 851–863 (1999).

    Article  CAS  Google Scholar 

  63. Bagrodia, S. & Cerione, R. A. PAK to the future . Trends Cell Biol. 9, 350– 355 (1999).

    Article  CAS  Google Scholar 

  64. Hall, A. Rho GTPases and the actin cytoskeleton. Science 279 , 509–514 (1998).

    Article  CAS  Google Scholar 

  65. Manser, E. et al. PAK kinases are directly coupled to the PIX family of nucleotide exchange factors. Mol. Cell 1, 183– 192 (1998).

    Article  CAS  Google Scholar 

  66. Zhao, Z. S., Manser, E. & Lim, L. Interaction between PAK and nck: a template for Nck targets and role of PAK autophosphorylation. Mol. Cell. Biol. 20, 3906–3917 (2000).

    Article  CAS  Google Scholar 

  67. Sells, M. A. et al. Human p21-activated kinase (Pak1) regulates actin organization in mammalian cells. Curr. Biol. 7, 202– 210 (1997).

    Article  CAS  Google Scholar 

  68. Manser, E. et al. Expression of constitutively active alpha-PAK reveals effects of the kinase on actin and focal complexes. Mol. Cell. Biol. 17, 1129–1143 (1997).

    Article  CAS  Google Scholar 

  69. Donaldson, J. G. & Klausner, R. D. ARF: a key regulatory switch in membrane traffic and organelle structure. Curr. Opin. Cell Biol. 6, 527–532 (1994).

    Article  CAS  Google Scholar 

  70. D'Souza-Schorey, C., Boshans, R. L., McDonough, M., Stahl, P. D. & Van Aelst, L. A role for POR1, a Rac1-interacting protein, in ARF6-mediated cytoskeletal rearrangements . EMBO J. 16, 5445–5454 (1997).

    Article  CAS  Google Scholar 

  71. Radhakrishna, H., Al-Awar, O., Khachikian, Z. & Donaldson, J. G. ARF6 requirement for Rac ruffling suggests a role for membrane trafficking in cortical actin rearrangements. J. Cell Sci. 112, 855–866 ( 1999).

    CAS  PubMed  Google Scholar 

  72. Norman, J. C. et al. ARF1 mediates paxillin recruitment to focal adhesions and potentiates Rho-stimulated stress fiber formation in intact and permeabilized Swiss 3T3 fibroblasts. J. Cell Biol. 143, 1981–1995 (1998).

    Article  CAS  Google Scholar 

  73. Vitale, N. et al. GIT proteins, A novel family of phosphatidylinositol 3,4,5-trisphosphate-stimulated GTPase-activating proteins for ARF6. J. Biol. Chem. 275, 13901–13906 (2000).

    Article  CAS  Google Scholar 

  74. Brown, M. T. et al. ASAP1, a phospholipid-dependent Arf GTPase-activating protein that associates with and is phosphorylated by Src. Mol. Cell. Biol. 18, 7038–7051 ( 1998).

    Article  CAS  Google Scholar 

  75. Randazzo, P. A. et al. The Arf GTPase-activating protein ASAP1 regulates the actin cytoskeleton. Proc. Natl Acad. Sci. USA 97, 4011–4016 (2000).

    Article  CAS  Google Scholar 

  76. Andreev, J. et al. Identification of a new Pyk2 target protein with Arf-GAP activity . Mol. Cell. Biol. 19, 2338– 2350 (1999).

    Article  CAS  Google Scholar 

  77. Kondo, A. et al. A new paxillin-binding protein, PAG3/Papalpha/KIAA0400, bearing an ADP-ribosylation factor GTPase-activating protein activity, is involved in paxillin recruitment to focal adhesions and cell migration. Mol. Biol. Cell 11, 1315–1327 (2000).

    Article  CAS  Google Scholar 

  78. Igishi, T. et al. Divergent signaling pathways link focal adhesion kinase to mitogen- activated protein kinase cascades. Evidence for a role of paxillin in c- Jun NH(2)-terminal kinase activation. J. Biol. Chem. 274, 30738–30746 (1999).

    Article  CAS  Google Scholar 

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  1. Department of Cell and Developmental Biology, SUNY Upstate Medical University, 750 East Adams Street, Syracuse, 13210, New York, USA

    Christopher E. Turner

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Turner, C. Paxillin and focal adhesion signalling. Nat Cell Biol 2, E231–E236 (2000). https://doi.org/10.1038/35046659

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