Phosphatases in cell-matrix adhesion and migration

Nature Reviews Molecular Cell Biology

Volumn 4, Issue 9, 2003, Pages 700-711

  Larsen, Melinda ^a   Tremblay, Michel L ^b   Yamada, Kenneth M ^a  

^a NATIONAL INSTITUTE OF DENTAL AND CRANIOFACIAL RESEARCH   (United States)

^b MCGILL UNIVERSITY   (Canada)

Author keywords

[No Author keywords available]

Indexed keywords

ACTIN; PHOSPHATASE; PHOSPHOTRANSFERASE;

CELL ADHESION; CELL MIGRATION; CELL MOTILITY; CYTOSKELETON; DYNAMICS; ENZYME ACTIVITY; EXTRACELLULAR MATRIX; MOLECULAR BIOLOGY; PRIORITY JOURNAL; PROTEIN FOLDING; PROTEIN PHOSPHORYLATION; PROTEIN PROTEIN INTERACTION; REVIEW;

ACTINS; ANIMALS; CELL MOVEMENT; CELL-MATRIX JUNCTIONS; HUMANS; MONOMERIC GTP-BINDING PROTEINS; PHOSPHORIC MONOESTER HYDROLASES;

EID: 0041336899     PISSN: 14710072     EISSN: None     Source Type: Journal    
DOI: 10.1038/nrm1199     Document Type: Review

References (133)

1. Edwards, J. G., Campbell, G., Grierson, A. W. & Kinn, S. R. Vanadate inhibits both intercellular adhesion and spreading on fibronectin of BHK21 cells and transformed derivatives. J. Cell Sci. 98, 363-368 (1991). One of the first papers to show that phosphatases affect adhesion. They showed that vanadate inhibited both attachment and spreading in cell culture.
2. Wilson, A. K., Takai, A., Ruegg, J. C. & de Lanerolle, P. Okadaic acid, a phosphatase inhibitor, decreases macrophage motility. Am. J. Physiol. 260, L105-L112 (1991). One of the first papers to indicate that phosphatases affect cell migration. Using the fairly specific PP2A inhibitor okadaic acid, the authors showed that macrophage migration was inhibited. Significantly, they correlated cytoskeletal reorganization with inhibition of motility, indicating that phosphatases uncouple these highly coordinated processes.
3. Neel, B. G. & Tonks, N. K. Protein tyrosine phosphatases in signal transduction. Curr. Opin. Cell Biol. 9, 193-204 (1997).
4. Angers-Loustau, A., Côté, J. F. & Tremblay, M. L. Roles of protein tyrosine phosphatases in cell migration and adhesion. Biochem. Cell Biol. 77, 493-505 (1999).
5. Beltran, P. J. & Bixby, J. L. Receptor protein tyrosine phosphatases as mediators of cellular adhesion. Front. Biosci. 8, D87-D99 (2003).
6. Sheetz, M. P., Felsenfeld, D. P. & Galbraith, C. G. Cell migration: regulation of force on extracellular-matrix-integrin complexes. Trends Cell Biol. 8, 51-54 (1998).
7. Trinkaus, J. P. in Cells Into Organs: The Forces That Shape The Embryo, 2nd Edn, 179-226 (Prentice-Hall Inc., Englewood Cliffs, New Jersey, 1984).
8. Zebda, N. et al. Phosphorylation of ADF/cofilin abolishes EGF-induced actin nucleation at the leading edge and subsequent lamellipod extention. J. Cell Biol. 151, 1119-1128 (2000).
9. Ichetovkin, I., Grant, W. & Condeelis, J. Cofilin produces newly polymerized actin filaments that are preferred for dendritic nucleation by the Arp2/3 complex. Curr. Biol. 12, 79-84 (2002).
10. Dawe, H. R., Minamide, L. S., Bamburg, J. R. & Cramer, L. P. ADF/Cofilin controls cell polarity during fibroblast migration. Curr. Biol. 13, 252-257 (2003).
11. Niwa, R., Nagata-Ohashi, K., Takeichi, M., Mizuno, K. & Uemura, T. Control of actin reorganization by Slingshot, a family of phosphatases that dephosphorylate ADF/cofilin. Cell 108, 233-246 (2002).
12. Ambach, A. et al. The serine phosphatases PP1 and PP2A associate with and activate the actin-binding protein cofilin in human T lymphocytes. Eur J. Immunol. 30, 3422-3431 (2000).
13. Arber, S, et al. Regulation of actin dynamics through phosphorylation of cofilin by LIM-kinase. Nature 393, 805-809 (1998).
14. Maekawa, M, et al. Signaling from Rho to the actin cytoskeleton through protein kinases ROCK and LIM-kinase. Science 285, 895-898 (1999).
15. Ridley, A. J. & Hall, A. The small GTP-binding protein rho regulates the assembly of focal adhesions and actin stress fibers in response to growth factors. Cell 70, 389-399 (1992).
16. Ridley, A. J., Paterson, H. F., Johnston, C. L., Diekmann, D. & Hall, A. The small GTP-binding protein rac regulates growth factor-induced membrane ruffling. Cell 70, 401-410 (1992).
17. Kozma, R., Ahmed, S., Best, A. & Lim, L. The Ras-related protein Cdc42Hs and bradykinin promote formation of peripheral actin microspikes and filopodia in Swiss 3T3 fibroblasts. Mol. Cell. Biol. 15, 1942-1952 (1995).
18. Roof, R. W. et al. Phosphotyrosine (p-Tyr)-dependent and -independent mechanisms of p190 RhoGAP-p120 RasGAP interaction: Tyr 1105 of p190, a substrate for c-Src, is the sole p-Tyr mediator of complex formation. Mol. Cell. Biol. 18, 7052-7063 (1998).
19. Kodama, A. et al. Involvement of an SHP-2-Rho small G protein pathway in hepatocyte growth factor/scatter factor-induced cell scattering. Mol. Biol. Cell 11, 2565-2575 (2000).
20. Schoenwaelder, S. M. et al. The protein tyrosine phosphatase SHP-2 regulates RhoA activity. Curr. Biol. 10, 1523-1526 (2000).
21. Inagaki, K. et al. SHPS-1 regulates integrin-mediated cytoskeletal reorganization and cell motility. EMBO J. 19, 6721-6731 (2000).
22. Lacalle, R. A. et al. Specific SHP-2 partitioning in raft domains triggers integrin-mediated signaling via Rho activation. J. Cell Biol. 157, 277-289 (2002).
23. Motegi, S. et al. Role of the CD47-SHPS-1 system in regulation of cell migration. EMBO J. 22, 2634-2644 (2003).
24. Sastry, S. K., Lyons, P. D., Schaller, M. D. & Burridge, K. PTP-PEST controls motility through regulation of Rac1. J. Cell Sci. 115, 4305-4316 (2002).
25. Gu, J. et al. Shc and FAK differentially regulate cell motility and directionality modulated by PTEN. J. Cell Biol. 146, 389-403 (1999).
26. Li, D. M. & Sun, H. TEP1, encoded by a candidate tumor suppressor locus, is a novel protein tyrosine phosphatase regulated by transforming growth factor β. Cancer Res. 57, 2124-2129 (1997).
27. Liliental, J. et al. Genetic deletion of the Pten tumor suppressor gene promotes cell motility by activation of Rac1 and Cdc42 GTPases. Curr. Biol. 10, 401-404 (2000).
28. Shiota, M. et al. Protein tyrosine phosphatase PTP20 induces actin cytoskeleton reorganization by dephosphorylating p190 RhoGap in rat ovarian granulosa cells stimulated with FSH. Mol. Endocrinol. 4, 534-549 (2003).
29. Nimnual, A, S., Taylor, L. J. & Bar-Sagi, D. Redox-dependent downregulation of Rho by Rac. Nature Cell Biol. 5, 236-241 (2003).
30. Dharmawardhane, S., Sanders, L. C., Martin, S. S., Daniels, R. H. & Bokoch, G. M. Localization of p21-activated kinase 1 (PAK1) to pinocytic vesicles and cortical actin structures in stimulated cells. J. Cell Biol. 138, 1265-1278 (1997).
31. Sells, M. A. et al. Human p21-activated kinase (PAK1) regulates actin organization in mammalian cells. Curr. Biol. 7, 202-210 (1997).
32. Sanders, L. C., Matsumura, F., Bokoch, G. M. & de Lanerolle, P. Inhibition of myosin light chain kinase by p21-activated kinase. Science 283, 2083-2085 (1999).
33. Edwards, D. C., Sanders, L. C., Bokoch, G. M. & Gill, G. N. Activation of LIM-kinase by PAK1 couples Rac/Cdc42 GTPase signalling to actin cytoskeletal dynamics. Nature Cell Biol. 1, 253-259 (1999).
34. Koh,C. G., Tan, E. J., Manser, E. & Lim, L. The p21-activated kinase PAK is negatively regulated by POPX1 and POPX2, a pair of serine/threonine phosphatases of the PP2C family. Curr. Biol. 12, 317-321 (2002).
35. Beningo, K. A., Dembo, M., Kaverina, I., Small, J. V. & Wang, Y. L. Nascent focal adhesions are responsible for the generation of strong propulsive forces in migrating fibroblasts. J. Cell Biol. 153, 881-888 (2001).
36. Galbraith, C. G. & Sheetz. M. P. A micromachined device provides a new bend on fibroblast traction forces. Proc. Natl. Acad. Sci. USA 94, 9114-9118 (1997).
37. von Wichert, G. et al, RPTP-α acts as a transducer of mechanical force on αv/β3-integrin-cytoskeleton linkages. J. Cell Biol. 161, 143-153 (2003).
38. Schneider, G. B., Gilmore, A. P., Lohse, D. L., Romer, L. H. & Burridge, K. Microinjection of protein tyrosine phosphatases into fibroblasts disrupts focal adhesions and stress fibers. Cell Adhes. Commun. 5, 207-219 (1998).
39. 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).
40. Garton, A. J. & Tonks, N. K. Regulation of fibroblast motility by the protein tyrosine phosphatase PTP-PEST. J. Biol. Chem. 274, 3811-3818 (1999).
41. Zamir, E. & Geiger, B. Molecular complexity and dynamics of cell-matrix adhesions. J. Cell Sci. 114, 3583-3590 (2001).
42. Cary, L. A., Chang, J. F. & Guan, J. L. Stimulation of cell migration by overexpression of focal adhesion kinase and its association with Src and Fyn. J. Cell Sci. 109, 1787-1794 (1996).
43. Ilic, D. et al. Reduced cell motility and enhanced focal adhesion contact formation in cells from FAK-deficient mice. Nature 377, 539-544 (1995).
44. Yu, D. H., Qu, C. K., Heneganu, O., Lu, X. & Feng, G. S. Protein-tyrosine phosphatase SHP-2 regulates cell spreading, migration, and focal adhesion. J. Biol. Chem. 273, 21125-21131 (1998).
45. Miao, H., Burnett, E., Kinch, M., Simon, E. & Wang, B. Activation of EphA2 kinase suppresses integrin function and causes focal-adhesion-kinase dephosphorylation. Nature Cell Biol. 2, 62-69 (2000).
46. Tamura, M. et al. PTEN interactions with focal adhesion kinase and suppression of the extracellular matrix-dependent phosphatidylinositol 3-kinase/Akt cell survival pathway. J. Biol. Chem. 274, 20693-20703 (1999).
47. Fresu, M., Bianchi, M., Parsons, J. T. & Villa-Moruzzi, E. Cell-cycle-dependent association of protein phosphatase 1 and focal adhesion kinase. Biochem. J. 358, 407-414 (2001).
48. 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).
49. Ito, A. et al. A truncated isoform of the PP2A B56 subunit promotes cell motility through paxillin phosphorylation. EMBO J. 19, 562-571 (2000).
50. Jackson, J. L. & Young, M. R. Protein phosphatase-2A modulates the serine and tyrosine phosphorylation of paxillin in Lewis lung carcinoma tumor variants. Clin. Exp. Metastasis 19, 409-415 (2002).
51. Pixley, F. J., Lee, P. S., Condeelis, J. S. & Stanley, E. R. Protein tyrosine phosphatase φ regulates paxillin tyrosine phosphorylation and mediates colony-stimulating factor 1-induced morphological changes in macrophages, Mol. Cell. Biol. 21, 1795-1809 (2001).
52. 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).
53. Côté, 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).
54. Zeng, L. et al. PTPα regulates integrin-stimulated FAK autophosphorylation and cytoskeletal rearrangement in cell spreading and migration. J. Cell Biol. 160, 137-146 (2003).
55. Young, M. R., Kolesiak, K. & Meisinger, J. Protein phosphatase-2A regulates endothelial cell motility and both the phosphorylation and the stability of focal adhesion complexes. Int. J. Cancer 100, 276-282 (2002).
56. Young, M. R., Liu, S. W. & Meisinger, J. Protein phosphatase-2A restricts migration of Lewis lung carcinoma cells by modulating the phosphorylation of focal adhesion proteins. Int. J. Cancer 103, 38-44 (2003).
57. Pankov, R. et al. Specific β1 integrin site selectively regulates Akt/PKB signaling via local activation of PP2A. J. Biol. Chem. 278, 18671-18681 (2003).
58. Bjorge, J. D., Pang, A. & Fujita, D. J. Identification of protein-tyrosine phosphatase 1B as the major tyrosine phosphatase activity capable of dephosphorylating and activating c-Src in several human breast cancer cell lines. J. Biol. Chem. 275, 41439-41446 (2000). Reports a relatively rare role of a phosphatase in protein activation. The authors show that PTP1B directly dephosphorylates and activates Src in vitro. They identified this interaction by purifying phosphatase activity from extracts of a breast cancer cell line containing both elevated Src and phosphatase activity.
59. Liu, F., Sells, M. A. & Chernoff, J. Protein tyrosine phosphatase 1B negatively regulates integrin signaling. Curr. Biol. 8, 173-176 (1998).
60. 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).
61. Kain, K. H. & Klemke, R. L. Inhibition of cell migration by Abl family tyrosine kinases through uncoupling of Crk-CAS complexes. J. Biol. Chem. 276, 16185-16192 (2001).
62. Garton, A. J., Flint, A. J. & Tonks, N. K. Identification of p130(Cas) as a substrate for the cytosolic protein tyrosine phosphatase PTP-PEST. Mol. Cell. Biol. 16, 6408-6418 (1996).
63. Cong, F. et al. Cytoskeletal protein PSTPIP1 directs the PEST-type protein tyrosine phosphatase to the c-Abl kinase to mediate Abl dephosphorylation. Mol. Cell 6, 1413-1423 (2000).
64. Noguchi, T. et al. Inhibition of cell growth and spreading by stomach cancer-associated protein-tyrosine phosphatase-1 (SAP-1) through dephosphorylation of p130cas. J. Biol. Chem. 276, 15216-15224 (2001).
65. Sattler, M. et al. SHIP1, an SH2 domain containing polyinositol-5-phosphatase, regulates migration through two critical tyrosine residues and forms a novel signaling complex with DOK1 and CRKL. J. Biol. Chem. 276, 2451-2458 (2001).
66. Tsuda, M. et al. Integrin-mediated tyrosine phosphorylation of SHPS-1 and its association with SHP-2. Roles of Fak and Src family kinases. J. Biol. Chem. 273, 13223-13229 (1998).
67. Shen, Y. et al. Activation of the Jnk signaling pathway by a dual-specificity phosphatase, JSP-1. Proc. Natl Acad. Sci. USA 98, 13613-13618 (2001).
68. Shin, E. Y., Kim, S. Y. & Kim, E. G. c-Jun N-terminal kinase is involved in motility of endothelial cell. Exp. Mol. Med. 33, 276-283 (2001).
69. Okagaki, T., Higashi-Fujime, S., Ishikawa, R., Takano-Ohmuro, H. & Kohama, K. In vitro movement of actin filaments on gizzard smooth muscle myosin: requirement of phosphorylation of myosin light chain and effects of tropomyosin and caldesmon. J. Biochem. 109, 858-866 (1991).
70. Alessi, D., MacDougall, L. K., Sola, M. M., Ikebe, M. & Cohen, P. The control of protein phosphatase-1 by targetting subunits. The major myosin phosphatase in avian smooth muscle is a novel form of protein phosphatase-1. Eur. J. Biochem. 210, 1023-1035 (1992).
71. Kawano, Y. et al. Phosphorylation of myosin-binding subunit (MBS) of myosin phosphatase by Rho-kinase in vivo. J. Cell Biol. 147, 1023-1038 (1999).
72. Worthylake, R. A., Lemoine, S., Watson, J. M. & Burridge, K. RhoA is required for monocyte tail retraction during transendothelial migration. J. Cell Biol. 154, 147-160 (2001).
73. Yoshinaga-Ohara, N., Takahashi, A., Uchiyama, T. & Sasada, M. Spatiotemporal regulation of moesin phosphorylation and rear release by Rho and serine/threonine phosphatase during neutrophil migration. Exp. Cell Res. 278, 112-122 (2002).
74. Iijima, M. & Devreotes, P. Tumor suppressor PTEN mediates sensing of chemoattractant gradients. Cell 109, 599-610 (2002).
75. Funamoto, S., Meili, R., Lee, S., Parry, L. & Firtel, R. A. Spatial and temporal regulation of 3-phosphoinositides by PI3-kinase and PTEN mediates chemotaxis. Cell 109, 611-623 (2002). References 74 and 75 identify a role for PTEN in directional migration through its lipid phosphatase activity. These studies both used Dictyostelium as a model system.
76. Iijima, M., Huang, Y. E. & Devreotes, P. Temporal and spatial regulation of chemotaxis. Dev. Cell 3, 469-478 (2002).
77. Chung, C. Y., Potikyan, G. & Firtel, R. A. Control of cell polarity and chemotaxis by Akt/PKB and PI3 kinase through the regulation of PAKa. Mol. Cell 7, 937-947 (2001).
78. Comer, F. I. & Parent, C. A. PI3-kinases and PTEN: how opposites chemoattract. Cell 109, 541-544 (2002).
79. Tamura, M. et al. Inhibition of cell migration, spreading, and focal adhesions by tumor suppressor PTEN. Science 280, 1614-1617 (1998).
80. Tamura, M., Gu, J., Takino, T. & Yamada, K. M. Tumor suppressor PTEN inhibition of cell invasion, migration, and growth: differential involvement of focal adhesion kinase and p130Cas. Cancer Res. 59, 442-449 (1999).
81. Gu, J., Tamura, M. &Yamada, K. M. Tumor suppressor PTEN inhibits integrin- and growth factor-mediated mitogen-activated protein (MAP) kinase signaling pathways. J. Cell Biol. 143, 1375-1383 (1998).
82. Spiegel, S., English, D. & Milstien, S. Sphingosine 1-phosphate signaling: providing cells with a sense of direction. Trends Cell Biol. 12, 236-242 (2002).
83. Takuwa, Y. Subtype-specific differential regulation of Rho family G proteins and cell migration by the Edg family sphingosine-1·phosphate receptors. Biochim. Biophys. Acta 1582, 112-120 (2002).
84. Desai, C. J., Gindhart, J. G. Jr, Goldstein, L. S. & Zinn, K. Receptor tyrosine phosphatases are required for motor axon guidance in the Drosophila embryo. Cell 84, 599-609 (1996).
85. Tan, C., Stronach, B. & Perrimon, N. Roles of myosin phosphatase during Drosophila development. Development 130, 671-681 (2003).
86. Saxton, T. M. et al. Abnormal mesoderm patterning in mouse embryos mutant for the SH2 tyrosine phosphatase SHP-2. EMBO J. 16, 2352-2364 (1997). In this paper, chimeric analysis was used to identify a role for SHP2 in mammalian limb development, which was not possible to determine in knockout embryos owing to defective gastrulation. The role of SHP2 in limb development is presumed to involve changes in cell shape, migration or adhesion.
87. Furuta, Y. et al. Mesodermal defect in late phase of gastrulation by a targeted mutation of focal adhesion kinase, FAK. Oncogene 11, 1989-1995 (1995).
88. Saxton, T. M. & Pawson, T. Morphogenetic movements at gastrulation require the SH2 tyrosine phosphatase SHP-2. Proc. Natl Acad. Sci. USA 96, 3790-3795 (1999).
89. Saxton, T. M. et al. The SH2 tyrosine phosphatase SHP-2 is required for mammalian limb development. Nature Genet. 24, 420-423 (2000).
90. Gotz, J., Probst, A., Ehler, E., Hemmings, B. & Kues, W. Delayed embryonic lethality in mice lacking protein phosphatase 2A catalytic subunit Cα. Proc. Natl Acad. Sci. USA 95, 12370-12375 (1998).
91. Li, L., Liu, F. & Ross, A. H. PTEN regulation of neural development and CNS stem cells. J. Cell. Biochem. 88, 24-28 (2003).
92. Schaapveld, R. Q. et al. Impaired mammary gland development and function in mice lacking LAR receptor-like tyrosine phosphatase activity. Dev. Biol. 188, 134-146 (1997).
93. Pulido, R., Serra-Pages, C., Tang, M. & Streuli, M. The LAR/PTPδ/PTPσ subfamily of transmembrane protein-tyrosine-phosphatases: multiple human LAR, PTPδ, and PTPσ isoforms are expressed in a tissue-specific manner and associate with the LAR-interacting protein LIP1. Proc. Natl Acad. Sci. USA 92, 11686-11690 (1995).
94. Harrington, R. J., Gutch, M. J., Hengartner, M. O., Tonks, N. K. & Chisholm, A. D. The C. elegans LAR-like receptor tyrosine phosphatase PTP-3 and the VAB-1 Eph receptor tyrosine kinase have partly redundant functions in morphogenesis. Development 129, 2141-2153 (2002).
95. Haj, F. G., Markova, B., Klaman, L. D., Bohmer, F. D. & Neel, B. G. Regulation of receptor tyrosine kinase signaling by protein tyrosine phosphatase-1B. J. Biol. Chem. 278, 739-744 (2003).
96. Manning, G., Whyte, D. B., Martinez, R., Hunter, T. & Sudarsanam, S. The protein kinase complement of the human genome. Science 298, 1912-1934 (2002).
97. Lander, E. S. et al. Initial sequencing and analysis of the human genome. Nature 409, 860-921 (2001).
98. Venter, J. C. et al. The sequence of the human genome. Science 291, 1304-1351 (2001).
99. Tonks, N. K. & Neel, B. G. Combinatorial control of the specificity of protein tyrosine phosphatases. Curr. Opin. Cell Biol. 13, 182-195 (2001).
100. Hubbard, M. J. & Cohen, P. On target with a new mechanism for the regulation of protein phosphorylation. Trends Biochem. Sci. 18, 172-177 (1993).
101. Denu, J. M. & Dixon, J. E. Protein tyrosine phosphatases: mechanisms of catalysis and regulation. Curr. Opin. Chem. Biol. 2, 633-641 (1998).
102. Espanel, X., Huguenin-Reggiani, M. & Van Huijsduijnen, R. H. The SPOT technique as a tool for studying protein tyrosine phosphatase substrate specificities. Protein Sci. 11, 2326-2334 (2002).
103. Xie, L., Zhang, Y. L. & Zhang, Z. Y. Design and characterization of an improved protein tyrosine phosphatase substrate-trapping mutant. Biochemistry 41, 4032-4039 (2002).
104. Meng, T. C., Fukada, T. & Tonks, N. K. Reversible oxidation and inactivation of protein tyrosine phosphatases in vivo. Mol. Cell 9, 387-399 (2002). One of the first papers to identify oxidation as a reversible post-translational modification of phosphatases. This discovery not only indicates a possible method for placement of phosphatases within specific signalling cascades, but also that this might be an important mechanism for the downregulation of phosphatase activity and consequent amplification of a tyrosine kinase signal.
105. Burke, T. R. Jr & Zhang, Z. Y. Protein-tyrosine phosphatases: structure, mechanism, and inhibitor discovery. Biopolymers 47, 225-241 (1998).
106. Huang, P. et al. Structure-based design and discovery of novel inhibitors of protein tyrosine phosphatases. Bioorg. Med. Chem. 11, 1835-1849 (2003).
107. Elbashir, S. M., Harborth, J., Weber, K. & Tuschl, T. Analysis of gene function in somatic mammalian cells using small interfering RNAs. Methods 26, 199-213 (2002).
108. Kirchner, J., Kam, Z., Tzur, G., Bershadsky, A. D. & Geiger, B. Live-cell monitoring of tyrosine phosphorylation in focal adhesions following microtubule disruption. J. Cell Sci. 116, 975-986 (2003).
109. Zhang, J., Ma, Y., Taylor, S. S. & Tsien, R. Y. Genetically encoded reporters of protein kinase A activity reveal impact of substrate tethering. Proc. Natl Acad. Sci. USA 98, 14997-15002 (2001). This innovative study makes use of a reporter construct to image the localization and dynamics of serine/threonine kinase and phosphatase activity in live cells by fluorescence resonance energy transfer (FRET).
110. Ting, A. Y., Kain, K. H., Klemke, R. L. & Tsien, R. Y. Genetically encoded fluorescent reporters of protein tyrosine kinase activities in living cells, Proc. Natl Acad. Sci. USA 98, 15003-15008 (2001). This study confirms that the FRET technique for studying the localization of kinase/phosphatase activity in live cells developed by reference109 is applicable to tyrosine kinases and phosphatases.
111. Simpson, L. & Parsons, R. PTEN: life as a tumor suppressor. Exp. Cell Res. 264, 29-41 (2001).
112. van Huijsduijnen, R. H., Bombrun, A. & Swinnen, D. Selecting protein tyrosine phosphatases as drug targets. Drug Discov. Today 7, 1013-1019 (2002).
113. Andersen, J. N. et al. Structural and evolutionary relationships among protein tyrosine phosphatase domains. Mol. Cell. Biol. 21, 7117-7136 (2001). This review provides an excellent overview of the structure, function and evolutionary relationships among the PTP family members (see also Phosphatases in Online links).
114. Keyse, S. M. Protein phosphatases and the regulation of mitogen-activated protein kinase signalling. Curr. Opin. Cell Biol. 12, 186-192 (2000).
115. Mauro, L. J. & Dixon, J. E. 'Zip codes' direct intracellular protein tyrosine phosphatases to the correct cellular 'address'. Trends Biochem. Sci, 19, 151-155 (1994).
116. Barford, D., Das, A. K. & Egloff, M. P. The structure and mechanism of protein phosphatases: insights into catalysis and regulation. Annu. Rev. Biophys. Biomol. Struct. 27, 133-164 (1998).
117. Rohrschneider, L. R., Fuller, J. F., Wolf, I., Liu, Y. & Lucas, D. M. Structure, function, and biology of SHIP proteins. Genes Dev. 14, 505-520 (2000).
118. Cohen, P. The origins of protein phosphorylation. Nature Cell Biol. 4, E127-E130 (2002). This article gives an excellent history of the discovery of cellular protein phosphorylation.
119. Harder, K. W., Moller, N. P., Peacock, J. W. & Jidk, F. R. Protein-tyrosine phosphatase α regulates Src family kinases and alters cell-substratum adhesion. J. Biol. Chem. 273, 31890-31900 (1998).
120. Palka, H. L., Park, M. & Tonks, N. K. Hepatocyte growth factor receptor tyrosine kinase Met is a substrate of the receptor protein-tyrosine phosphatase DEP-1. J. Biol. Chem. 278, 5728-5735 (2003).
121. Muller, T., Choidas, A., Reichmann, E. & Ullrich, A. Phosphorylation and free pool of β-catenin are regulated by tyrosine kinases and tyrosine phosphatases during epithelial cell migration. J. Biol. Chem. 274, 10173-10183 (1999).
122. Hart, M. J., de los Santos, R., Albert, I. N., Rubinfeld, B. & Polakis, P. Downregulation of β-catenin by human axin and its association with the APC tumor suppressor, β-catenin and GSK3β. Curr. Biol. 8, 573-581 (1998).
123. Polakis, P. Wnt signaling and cancer. Genes Dev. 14, 1837-1851 (2000).
124. Muller, T., Bain, G., Wang, X. & Papkoff, J. Regulation of epithelial cell migration and tumor formation by β-catenin signaling. Exp. Cell Res. 280, 119-133 (2002).
125. Persad, S., Troussard, A. A., McPhee, T. R., Mulholland, D. J. & Dedhar, S. Tumor suppressor PTEN inhibits nuclear accumulation of β-catenin and T cell/lymphoid enhancer factor 1-mediated transcriptional activation. J. Cell Biol. 153, 1161-1174 (2001).
126. Johnson, K. G. & Van Vactor, D. Receptor protein tyrosine phosphatases in nervous system development. Physiol. Rev. 83, 1-24 (2003).
127. Janssens, V. & Goris, J. Protein phosphatase 2A: a highly regulated family of serine/threonine phosphatases implicated in cell growth and signalling. Biochem. J. 353, 417-439 (2001).
128. Yu, X. X. et al. Methylation of the protein phosphatase 2A catalytic subunit is essential for association of B α regulatory subunit but not SG2NA, striatin, or polyomavirus middle tumor antigen. Mol. Biol. Cell 12, 185-199 (2001).
129. Wallace, M. J., Radd, C., Batt, J. & Rotin, D. The second catalytic domain of protein tyrosine phosphatase δ (PTPδ) binds to and inhibits the first catalytic domain of PTPσ, Mol. Cell. Biol. 18, 2608-2616 (1998).
130. Desai, D. M., Sap, J., Schlessinger, J. & Weiss, A. Ligand-mediated negative regulation of a chimeric transmembrane receptor tyrosine phosphatase. Cell 73, 541-554 (1993).
131. Lechleider, R. J. et al. Activation of the SH2-containing phosphotyrosine phosphatase SH-PTP2 by its binding site, phosphotyrosine 1009, on the human platelet-derived growth factor receptor. J. Biol. Chem. 268, 21478-21481 (1993).
132. Chen, J., Martin, B. L. & Brautigan, D. L. Regulation of protein serine-threonine phosphatase type-2A by tyrosine phosphorylation. Science 257, 1261-1264 (1992).
133. Lu, W., Gong, D., Bar-Sagi, D. & Cole, P. A. Site-specific incorporation of a phosphotyrosine mimetic reveals a role for tyrosine phosphorylation of SHP-2 in cell signaling. Mol. Cell 8, 759-769 (2001).