Rap1 signalling: Adhering to new models

Nature Reviews Molecular Cell Biology

Volumn 2, Issue 5, 2001, Pages 369-377

  Bos, Johannes L ^a   De Rooij, Johan ^a   Reedquist, Kris A ^a  

^a UNIVERSITY MEDICAL CENTER UTRECHT   (Netherlands)

Author keywords

[No Author keywords available]

Indexed keywords

RAP1 PROTEIN;

AMINO ACID SEQUENCE; ANIMAL; CHEMISTRY; HUMAN; MOLECULAR GENETICS; PHYSIOLOGY; REVIEW; SIGNAL TRANSDUCTION;

AMINO ACID SEQUENCE; ANIMALS; HUMANS; MOLECULAR SEQUENCE DATA; RAP1 GTP-BINDING PROTEINS; SIGNAL TRANSDUCTION;

EID: 0035347262     PISSN: 14710072     EISSN: None     Source Type: Journal    
DOI: 10.1038/35073073     Document Type: Review

References (99)

1. Kitayama, H., Sugimoto, Y., Matsuzaki, T., Ikawa, Y. & Noda, M. A ras-related gene with transformation suppressor activity. Cell 56, 77-84 (1989). Classic paper with the first description of a biological effect of Rap1 in the reversion of K-ras transformation.
2. Bos, J. L. All in the family? New insights and questions regarding interconnectivity of Ras, Rap1 and Ral. EMBO J. 17, 6776-6782 (1998).
3. 2+-mediated activation of Rap1 in human platelets. EMBO J. 16, 252-259 (1997). Paper describing a novel procedure for the detection of activated Rap1, which is now the method of choice.
4. Altschuler, D. L., Peterson, S. N., Ostrowski, M. C. & Lapetina, E. G. Cyclic AMP-dependent activation of Rap1b. J. Biol. Chem. 270, 10373-10376 (1995). First paper to show activation of Rap1 by cyclic AMP.
5. McLeod, S. J., lngham, R. J., Bos, J. L, Kurosaki, T. & Gold, M. R. Activation of the Rap1 GTPase by the B cell antigen receptor. J. Biol. Chem. 273, 29218-29223 (1998).
6. Zwartkruis, F. J., Wolthuis, R. M., Nabben, N. M., Franke, B. & Bos, J. L. Extracellular signal-regulated activation of Rap1 fails to interfere in Ras effector signalling. EMBO J. 17, 5905-5912 (1998).
7. York, R. D. et al. Role of phosphoinositide 3-kinase and endocytosis in nerve growth factor-induced extracellular signal-regulated kinase activation via ras and rap1. Mol. Cell. Biol. 20, 8069-8083 (2000).
8. Gotoh, T. et al. Identification of Rap1 as a target for the Crk SH3 domain-binding guanine nucleotide-releasing factor C3G. Mol. Cell. Biol. 15, 6746-6753 (1995).
9. Ichiba, T. et al. Activation of C3G guanine nucleotide exchange factor for Rap1 by phosphorylation of tyrosine 504, J. Biol. Chem. 274, 14376-14381 (1999).
10. Sakkab, D. et al. Signaling of hepatocyte growth factor/scatter factor (HGF) to the small GTPase Rap1 via the large docking protein Gab1 and the adapter protein CRKL. J. Biol. Chem. 275, 10772-10778 (2000).
11. Gotoh, T. et al. Activation of R-Ras by Ras-guanine nucleotide-releasing factor. J. Biol. Chem. 272, 18602-18607 (1997).
12. Mochizuki, N. et al. Crk activation of JNK via C3G and R-Ras. J. Biol. Chem. 275, 12667-12671 (2000).
13. de Rooij, J. et al. Epac is a Rap1 guanine-nucleotide-exchange factor directly activated by cyclic AMP. Nature 396, 474-477 (1998).
14. Kawasaki, H. et al. A family of cAMP-binding proteins that directly activate Rap1. Science 282, 2275-2279 (1998). References 13 and 14 were the first papers to show that a Rap1GEF is a genuine target for cAMP.
15. de Rooij, J. et al. Mechanism of regulation of the Epac family of cAMP-dependent RapGEFs. J. Biol. Chem. 275, 20829-20836 (2000).
16. Ozaki, N. et al. cAMP-GEFII is a direct target of cAMP in regulated exocytosis. Nature Cell Biol. 2, 805-811 (2000).
17. Ichiba, T., Hoshi, Y., Eto, Y., Tajima, N. & Kuraishi, Y. Characterization of GFR, a novel guanine nucleotide exchange factor for Rap1. FEBS Lett. 457, 85-69 (1999).
18. Rebhun, J. F., Castro, A. F. & Quilliam, L. A. Identification of guanine nucleotide exchange factors (GEFs) for the Rap1 GTPase. Regulation of MR-GEF by M-Ras-GTP interaction. J. Biol. Chem, 275, 34901-34908 (2000).
19. Kawasaki, H. et al. A Rap guanine nucleotide exchange factor enriched highly in the basal ganglia. Proc. Natl Acad. Sci. USA 95, 13278-13283 (1998).
20. Yamashita, S. et al. CalDAG-GEFIII activation of Ras. R-Ras, and Rap1. J. Biol. Chem. 275, 25488-25493 (2000).
21. Ebinu, J. O. et al. RasGRP, a Ras guanyl nucleotide-releasing protein with calcium-and diacylglycerol-binding motifs. Science 280, 1082-1086 (1998).
22. de Rooij, J. et al. PDZ-GEF1, a guanine nucleotide exchange factor specific for Rap1 and Rap2. J. Biol. Chem. 274, 38125-38130 (1999).
23. Ohtsuka. T. et al. nRap GEP: a novel neural GDP/GTP exchange protein for rap1 small G protein that interacts with synaptic scaffolding molecule (S-SCAM). Biochem. Biophys. Res. Commun. 265, 38-44 (1999).
24. Liao, Y. et al. RA-GEF, a novel Rap1A guanine nucleotide exchange factor containing a Ras/Rap1A-associating domain, is conserved between nematode and humans. J. Biol. Chem. 274, 37815-37820 (1999).
25. Kawajiri, A. et al. Identification of a novel β-catenininteracting protein. Biochem. Biophys. Res. Commun. 273, 712-717 (2000).
26. Gotoh, T., Cai, D., Tian, X., Feig, L. A. & Lerner, A. p130Cas regulates the activity of AND-34, a novel Ral, Rap1, and R-Ras guanine nucleotide exchange factor. J. Biol. Chem. 275, 30118-30123 (2000).
27. Polakis, P. G., Rubinfeld, B., Evans, T. & McCormick, F. Purification of a plasma membrane-associated GTPase-activating protein specific for rap1/Krev-1 from HL60 cells. Proc. Natl Acad. Sci. USA 88, 239-243 (1991).
28. Mochizuki, N. et al. Activation of the ERK/MAPK pathway by an isoform of rap1GAP associated with Ga(i). Nature 400, 891-894 (1999).
29. Meng, J., Glick, J. L., Polakis, P. & Casey, P. J. Functional interaction between Gα(z) and Rap1GAP suggests a novel form of cellular cross-talk. J. Biol. Chem. 274, 36663-36669 (1999). References 28 and 29 show that Rap1GAP interacts with the a-subunit of Gi/Gz family members, resulting In the activation of Rap1GAP.
30. Jordan, J. D., Carey, K. D., Stork, P. J. & Iyengar, R. Modulation of Rap activity by direct interaction of Gα(o) with Rap1 GTPase-activating protein. J. Biol. Chem. 274, 21507-21510 (1999).
31. Kurachi, H. et al. Human SPA-1 gene product selectively expressed in lymphoid tissues is a specific GTPase-activating protein for Rap1 and Rap2. Segregate expression profiles from a rap1GAP gene product. J. Biol. Chem. 272, 28081-28088 (1997).
32. Gao, O., Srinivasan, S., Boyer, S. N., Wazer, D. E. & Band, V. The E6 oncoproteins of high-risk papillomaviruses bind to a novel putative GAP protein, E6TP1, and target it for degradation. Mol. Cell. Biol. 19, 733-744 (1999). This paper shows a potential link between the Rap1 signalling pathway and papilloma-induced neoplasia.
33. Wienecke, R., Konig, A. & DeClue, J. E. Identification of tuberin, the tuberous sclerosis-2 product. Tuberin possesses specific Rap1GAP activity. J. Biol. Chem. 270, 16409-16414 (1995).
34. Xiao, G. H., Shoarinejad, F., Jin, F., Golemis, E. A. & Yeung, R. S. The tuberous sclerosis 2 gene product, tuberin, functions as a Rab5 GTPase activating protein (GAP) in modulating endocytosis. J. Biol. Chem. 272, 6097-6100 (1997).
35. 4-binding protein as a member of the GAP1 family. Nature 376, 527-530 (1995).
36. Ohba, Y. et al. Rap2 as a slowly responding molecular switch in the Rap1 signaling cascade. Mol. Cell. Biol. 20, 6074-6083 (2000).
37. Herrmann, C., Horn, G., Spaargaren, M. & Wittinghofer, A. Differential interaction of the ras family GTP-binding proteins H-Ras, Rap1 A, and R-Ras with the putative effector molecules Raf kinase and Ral-guanine nucleotide exchange factor. J. Biol. Chem. 271, 6794-6800 (1996).
38. Okada, T. et al. The strength of interaction at the Raf cysteine-rich domain is a critical determinant of response of Raf to Ras family small GTPases. Mol. Cell. Biol. 19, 6057-6064 (1999).
39. Okada, S., Matsuda, M., Anafi, M., Pawson, T. & Pessin, J. E. Insulin regulates the dynamic balance between Ras and Rap1 signaling by coordinating the assembly states of the Grb2-SOS and CrkII-CSG complexes. EMBO J. 17, 2554-2565 (1998).
40. Boussiotis, V. A., Freeman, G. J., Berezovskaya, A., Barber, D. L. & Nadler, L. M. Maintenance of human T cell anergy: blocking of IL-2 gene transcription by activated Rap1. Science 278, 124-128 (1997).
41. Carey, K. D. et al. CD28 and the tyrosine kinase lck stimulate mitogen-activated protein kinase activity in T cells via inhibition of the small G protein rapl. Mol. Cell. Biol. 20, 8409-8419 (2000).
42. Cook, S. J., Rubinfeld, B., Albert, I. & McCormick, F. RapV12 antagonizes Ras-dependent activation of ERK1 and ERK2 by LPA and EGF in Rat-1 fibroblasts. EMBO J. 12, 3475-3485 (1993).
43. Palsson, E. M., Popoff, M., Thelestam, M. & O'Neill, L. A. Divergent roles for Ras and Rap in the activation of p38 mitogen-activated protein kinase by interteukin-1. J. Biol. Chem. 275, 7818-7825 (2000).
44. Wu, J. et al. Inhibition of the EGF-activated MAP kinase signaling pathway by adenosine 3′,5′-monophosphate. Science 262, 1065-1069 (1993).
45. Ramstad, C., Sundvold, V, Johansen, H. K. & Lea, T. cAMP-dependent protein kinase (PKA) inhibits T cell activation by phosphorylating ser-43 of raf-1 in the MAPK/ERK pathway. Cell Signalling 12, 557-563 (2000).
46. Sidovar, M. F. et al. Phosphorylation of serine 43 is not required for inhibition of c-Raf kinase by the cAMP-dependent protein kinase. J. Biol. Chem. 275, 28688-28694 (2000).
47. Ohtsuka, T., Shimizu, K., Yamamori, B., Kuroda, S. & Takai, Y. Activation of brain B-Raf protein kinase by Rap1 B small GTP-binding protein. J. Biol. Chem. 271, 1258-1261 (1996).
48. Vossler, M. R. et al. CAMP activates MAP kinase and Elk-1 through a B-Raf-and Rap1 -dependent pathway. Cell 89, 73-82 (1997). First article to show that B-raf is a downstream target of Rap1.
49. York, R. D. et al. Rap1 mediates sustained MAP kinase activation induced by nerve growth factor. Nature 392, 622-626 (1998).
50. Okada, S. & Pessin, J. E. Insulin and epidermal growth factor stimulate a conformational change in Rap1 and dissociation of the Crkll-C3G complex. J. Biol. Chem. 272, 28179-28182 (1997).
51. Schmitt, J. M. & Stork, P. J. β2-adrenergic receptor activates extracellular signal-regulated kinases (ERKs) via the small G protein Rap1 and the serine/threonine kinase B-Raf. J. Biol. Chem. 275, 25342-25350 (2000).
52. Grewal, S. S. et al. Neuronal calcium activates a Rap1 and B-Raf signaling pathway via the cyclic adenosine monophosphate-dependent protein kinase. J. Biol. Chem. 275, 3722-3728 (2000).
53. Zanassi, P. et al. Cyclic AMP-dependent protein kinase induces CREB phosphorylation via an intracellular calcium release/ERK-dependent pathway in striatal neurons. J. Biol. Chem. 276, 11487-11495 (2001).
54. Tsygankova, O. M., Saaveddra, A., Rebhun, J. F., Quilliam, L. A. & Meinkoth, J. L. Coordinated regulation of Rap1 and thyroid differentiation by cAMP and protein kinase A. Mol. Cell. Biol. 21, 1921-1929 (2001).
55. Dremier, S. et al. Activation of the small G protein Rap1 in dog thyroid cells by both cAMP-dependent and-independent pathways. Biochem. Biophys. Res. Commun. 267, 7-11 (2000).
56. Busca, R. et al. Ras mediates the cAMP-dependent activation of extracellular signal-regulated kinases (ERKs) in melanocytes. EMBO J. 19, 2900-2910 (2000).
57. Saxena, M., Williams, S., Tasken, K. & Mustelin, T. Crosstalk between cAMP-dependent kinase and MAP kinase through a protein tyrosine phosphatase. Nature Cell Biol. 1, 305-311 (1999).
58. Qiu, W., Zhuang, S., von Lintig, F. C., Boss, G. R. & Pilz, R. B. Cell type-specific regulation of B-Raf kinase by cAMP and 14-3-3 proteins. J. Biol. Chem. 275, 31921-31929 (2000).
59. Lerosey, I., Pizon, V., Tavitian, A. & de Gunzburg, J. The cAMP-dependent protein kinase phosphorylates the rapl protein in vitro as well as in intact fibroblasts, but not the closely related rap2 protein. Biochem. Biophys. Res. Commun. 175, 430-436 (1991).
60. Polakis, P., Rubinfeld, B. & McCormick, F. Phosphorylation of rap1GAP in vivo and by cAMP-dependent kinase and the cell cycle p34cdc2 kinase in vitro. J. Biol. Chem. 267, 10780-10785 (1992).
61. Kishida, S. et al. Colocalization of Ras and RaI on the membrane is required for Ras-dependent RaI activation through Ral GDP dissociation stimulator. Oncogene 15, 2899-2907 (1997).
62. Reedquist, K. A. et al. The small GTPase, Rap1. mediates CD31-induced integrin adhesion. J. Cell Biol. 148, 1151-1158 (2000). Together with references 67 and 72, the first paper to show that Rap1 functions in the regulation of integrin activation.
63. Unnemann, T. et al. Thermodynamic and kinetic characterization of the interaction between the Ras binding domain of AF6 and members of the Ras subfamily. J. Biol. Chem. 274, 13556-13562 (1999).
64. Taya, S. et al. The Ras target AF-6 is a substrate of the fam deubiquitinating enzyme. J. Cell Biol. 142, 1053-1062 (1998).
65. Boettner, B., Govek, E. E., Cross, J. & Van Aelst, L. The junctional multidomain protein AF-6 is a binding partner of the Rapl A GTPase and associates with the actin cytoskeletal regulator profilin. Proc. Natl Acad. Sci. USA 97, 9064-9069 (2000).
66. Yamamoto, T., Harada, N., Kawano, Y., Taya, S. & Kaibuchi, K. In vivo interaction of AF-6 with activated Ras and ZO-1. Biochem. Biophys. Res. Commun. 259, 103-107 (1999).
67. Katagiri, K. et al. Rap1 is a potent activation signal for leukocyte function-associated antigen 1 distinct from protein kinase C and phosphatidylinositol-3-OH kinase Mol. Cell. Biol. 20, 1956-1969 (2000). Together with references 62 and 72, the first paper to show that Rap1 regulates integrin activation.
68. O'Rourke, A. M., Shao, H. & Kaye, J. A role for p21 ras/MAP kinase in TCR-mediated activation of LFA-1. J. Immunol. 161, 5800-5803 (1998).
69. Tanaka, Y. et al. H-Ras signals to cytoskeletal machinery in induction of integrin-mediated adhesion of T cells. J. Immunol. 163, 6209-6216 (1999).
70. Arai, A. et al. Rap1 is activated by erythropoietin or interleukin-3 and is involved in regulation of β1 integrin-mediated hematopoietic cell adhesion. J. Biol. Chem. 276, 10453-10462 (2001).
71. Tsukamoto, N., Hattori, M., Yang, H., Bos, J. L. & Minato, N. Rap1 GTPase-activating protein SPA-1 negatively regulates cell adhesion. J. Biol. Chem. 274, 18463-18469 (1999).
72. Caron, E., Self, A. J. & Hall, A. The GTPase Rap1 controls functional activation of macrophage integrin αMβ2 by LPS and other inflammatory mediators. Curr. Biol. 10, 974-978 (2000). Together with references 62 and 67, the first paper to show that Rap1 regulates integrin activation.
73. Schmidt, A., Caron, E. & Hall, A. Lipopolysaccharide-induced activation of p2-integrin function in macrophages requires irak kinase activity, p38 mitogen-activated protein kinase, and the rap1 GTPase. Mol. Cell. Biol. 21, 438-448 (2001).
74. Seastone, D. J. et al. The small Mr Ras-like GTPase Rap1 and the phospholipase C pathway act to regulate phagocytosis in Dictyostelium discoideum. Mol. Biol. Cell 10, 393-406 (1999).
75. Uemura, N. & Griffin, J. D. The adapter protein Crkl links Cbl to C3G after integrin ligation and enhances cell migration. J. Biol. Chem. 274, 37525-37532 (1999).
76. Franke, B. et al. Sequential regulation of the small GTPase Rap1 in human platelets. Mol. Cell. Biol. 20, 779-785 (2000).
77. Posern, G., Weber, C. K., Rapp, U. R. & Feller, S. M. Activity of Rap1 is regulated by bombesin, cell adhesion, and cell density in NIH3T3 fibroblasts. J. Biol. Chem. 273, 24297-24300 (1998).
78. Buensuceso, C. S. & O'Toole, T. E. The association of CRKII with C3G can be regulated by integrins and defines a novel means to regulate the mitogen-activated protein kinases. J. Biol. Chem. 275, 13118-13125 (2000).
79. Mochizuki, N. et al. Spatio-temporal images of growth factor induced activation of Ras and Rap1. Nature (in the press). First paper showing the localized activation of Rap1, using an elegant fluorescent resonance energy transfer procedure.
80. Dupuy, A. J., Morgan, K. & Largaespada, D. A. Activation of the Rap1 guanine nucleotide exchange gene, CalDAG-GEFI, in BXH2 murine myeloid leukemia. J. Biol. Chem. 276, 11804-11811 (2001).
81. Pizon, V., Desjardins, M., Bucci, C., Parton, R. G. & Zerial, M. Association of Rap1 a and Rap1 b proteins with late endocytic/phagocytic compartments and Rap2a with the Golgi complex. J. Cell Sci. 107, 1661-1670 (1994).
82. Quinn, M. T., Mullen, M. L., Jesaitis. A. J. & Linner, J. G. Subcellular distribution of the Rap1 A protein in human neutrophils: colocalization and cotranslocation with cytochrome b559. Blood 79, 1563-1573 (1992).
83. Maridonneau-Parini, I. & de Gunzburg, J. Association of rap1 and rap2 proteins with the specific granules of human neutrophils. Translocation to the plasma membrane during cell activation. J. Biol. Chem. 267, 6396-6402 (1992).
84. D'Silva, N. J., Jacobson, K. L. Ott, S. M. & Watson, E. L. p-adrenergic-induced cytosolic redistribution of Rap1 in rat parotid acini: role in secretion. Am. J. Physiol. 274, C1667-C1673 (1998).
85. McCabe, P. C., Haubruck, H., Polakis, P., McCormick, F. & Innis, M. A. Functional interaction between p21rap1A and components of the budding pathway in Saccharomyces cerevisiae. Mol. Cell. Biol. 12, 4084-4092 (1992).
86. Park, H. O., Sanson, A. & Herskowitz, I. Localization of bud2p, a GTPase-activating protein necessary for programming cell polarity in yeast to the presumptive bud site. Genes Dev. 13, 1912-1917 (1999). Paper showing that regulatory proteins of the yeast Rap1 orthologue Bud1, like the GAP Bud2, are involved in recognizing positional landmarks.
87. Park, H. O., Sanson, A. & Herskowitz. I. Localization of bud2p, a GTPase-activating protein necessary for programming cell polarity in yeast to the presumptive bud site. Genes Dev. 13, 1912-1917 (1999).
88. Gulli, M.-P. & Peter, M. Temporal and spatial regulation of Rho-type guanine nucleotide exchange factors: the yeast perspective. Genes Dev. 15, 365-379 (2001). Excellent review on the role of small GTPases in determining cell polarity.
89. Yaar, L., Mevarech, M. & Koltin, Y. A. Candida albicans RAS-related gene (CaRSR1) is involved in budding, cell morphogenesis and hypha development. Microbiology 143, 3033-3044 (1997).
90. Rebstein, P. J., Cardelli, J., Weeks, G. & Spiegelman, G. B. Mutational analysis of the role of Rap1 in regulating cytoskeletal function in Dictyostelium. Exp. Cell Res. 231, 276-283 (1997).
91. Hariharan, I. K., Carthew, R. W. & Rubin, G. M. The Drosophila roughened mutation: activation of a rap homolog disrupts eye development and interferes with cell determination. Cell 67, 717-722 (1991).
92. Asha, H., de Ruiter, N. D., Wang, M. G. & Hariharan, I. K. The Rap1 GTPase functions as a regulator of morphogenesis in vivo. EMBO J. 18, 605-615 (1999). Paper describing the possible function of Drosophila melanogaster Rap1 in morphogenesis, independently of Ras-mediated signalling.
93. Ishimaru, S., Williams, R., Clark, E., Hanafusa, H. & Gaul, U. Activation of the Drosophila C3G leads to cell fate changes and overproliferation during development, mediated by the RAS-MAPK pathway and RAP1. EMBO J. 18, 145-155 (1999).
94. Chen, F., Barkett, M., Ram, K. T., Quintanilla, A. & Hariharan, I. K. Biological characterization of Drosophila RapGap1, a GTPase activating protein for Rap1. Proc. Natl Acad. Sci. USA 94, 12485-12490 (1997).
95. 2+ATPase isoform 3b and Rap 1b: interrelation and regulation in physiopathology. Biochem. J. 332, 173-181 (1998).
96. Anneren, C., Reedquist, K. A., Bos, J. L. & Welsh, M. GTK, a Src-related tyrosine kinase, induces nerve growth factor-independent neurite outgrowth in PC12 cells through activation of the Rap1 pathway. Relationship to Shb tyrosine phosphorylation and elevated levels of focal adhesion kinase. J. Biol. Chem. 275, 29153-29161 (2000).
97. Lu, L., Anneren, C., Reedquist, K. A., Bos, J. L. & Welsh, M. NGF-dependent neurite outgrowth in PC12 cells overexpressing the Src homology 2-domain protein shb requires activation of the Rap1 pathway. Exp. Cell Res. 259, 370-377 (2000).
98. Altschuler, D. L. & Ribeiro-Neto, F. Mitogenic and oncogenic properties of the small G protein Rap1b. Proc. Natl Acad. Sci. USA 95, 7475-7479 (1998).
99. Pacold, M. E. et al. Crystal structure and functional analysis of ras binding to its effector phosphoinositide 3-kinase γ. Cell 103, 931-943 (2000).