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Adaptor protein APS binds the NH2-terminal autoinhibitory domain of guanine nucleotide exchange factor Vav3 and augments its activity

Oncogene volume 21, pages 7720–7729 (2002)Cite this article

Abstract

The N-terminal calponin homology (CH) domain of Vav guanine nucleotide exchange factor is thought to serve a regulatory role in the autoinhibition, however, its precise function is not entirely clear. We found that the adaptor molecule APS could bind the CH domain of Vav3, a member of the vav proto-oncogene family. The binding of Vav3 and APS was apparently stabilized by the tyrosine phosphorylation of Vav3 by Lck, and the association of APS with Vav3 in turn enhanced the Lck-mediated phosphorylation of Vav3. Focus formation assays demonstrated that APS could increase the transforming activity of proto-Vav3. Further analyses revealed that the Vav3 CH domain could bind the pleckstrin homology (PH) domain of APS and that this binding was indispensable to enhance the transforming activity of Vav3. We present here a novel stimulatory mechanism of Vav3 in which APS directly relieves the autoinhibitory CH domain and furthermore enhances its tyrosine phosphorylation by Lck.

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References

  • Abe K, Rossman KL, Liu B, Ritola KD, Chiang D, Campbell SL, Burridge K, Der CJ . 2000 J. Biol. Chem. 275: 10141–10149

  • Abe K, Whitehead IP, O'Bryan JP, Der CJ . 1999 J. Biol. Chem. 274: 30410–30418

  • Adams JM, Houston H, Allen J, Lints T, Harvey R . 1992 Oncogene 7: 611–618

  • Aghazadeh B, Lowry WE, Huang XY, Rosen MK . 2000 Cell 102: 625–633

  • Alberts AS, Treisman R . 1998 EMBO J. 17: 4075–4085

  • Bhattacharyya R, Wedegaertner PB . 2000 J. Biol. Chem. 275: 14992–14999

  • Bi F, Debreceni B, Zhu K, Salani B, Eva A, Zheng Y . 2001 Mol. Cell. Biol. 21: 1463–1474

  • Bustelo XR . 2000 Mol. Cell. Biol. 20: 1461–1477

  • Bustelo XR, Crespo P, Lopez-Barahona M, Gutkind JS, Barbacid M . 1997 Oncogene 15: 2511–2520

  • Castresana J, Saraste M . 1995 FEBS Lett. 374: 149–151

  • Cerione RA, Zheng Y . 1996 Curr. Opin. Cell Biol. 8: 216–222

  • Clark EA, Golub TR, Lander ES, Hynes RO . 2000 Nature 406: 532–535

  • Clark GJ, Cox AD, Graham SM, Der CJ . 1995 Methods Enzymol. 255: 395–412

  • Crespo P, Schuebel KE, Ostrom AA, Gutkind JS, Bustelo XR . 1997 Nature 385: 169–172

  • Das B, Shu X, Day GJ, Han J, Krishna ÃŒM, Falck JR, Broek D . 2000 J. Biol. Chem. 275: 15074–15081

  • De Sepulveda P, Ilangumaran S, Rottapel R . 2000 J. Biol. Chem. 275: 14005–14008

  • Deckert M, Tartare-Deckert S, Couture C, Mustelin T, Altman A . 1996 Immunity 5: 591–604

  • Doody GM, Bell SE, Vigorito E, Clayton E, McAdam S, Tooze R, Fernandez C, Lee IJ, Turner M . 2001 Nature Immunol. 2: 542–547

  • Gimona M, Winder SJ . 1998 Curr. Biol. 8: R674–R675

  • Habets GG, Scholtes EH, Zuydgeest D, van der Kammen RA, Stam JC, Berns A, Collard JG . 1994 Cell 77: 537–549

  • Hall A . 1998 Science 279: 509–514

  • Han J, Das B, Wei W, Van Aelst L, Mosteller RD, Khosravi-Far R, Westwick JK, Der CJ, Broek D . 1997 Mol. Cell. Biol. 17: 1346–1353

  • Han J, Luby-Phelps K, Das B, Shu X, Xia Y, Mosteller RD, Krishna ÃŒM, Falck JR, White MA, Broek D . 1998 Science 279: 558–560

  • Hart MJ, Jiang X, Kozasa T, Roscoe W, Singer WD, Gilman AG, Sternweis PC, Bollag G . 1998 Science 280: 2112–2114

  • Hobert O, Jallal B, Ullrich A . 1996 Mol. Cell. Biol. 16: 3066–3073

  • Horii Y, Beeler JF, Sakaguchi K, Tachibana M, Miki T . 1994 EMBO J. 13: 4776–4786

  • Inabe K, Ishiai M, Scharenberg AM, Freshney N, Downward J, Kurosaki T . 2002 J. Exp. Med. 195: 189–200

  • Iseki M, Takaki S, Takatsu K . 2000 Biochem. Biophys. Res. Commun. 272: 45–54

  • Katzav S, Cleveland JL, Heslop HE, Pulido D . 1991 Mol. Cell. Biol. 11: 1912–1920

  • Katzav S, Martin-Zanca D, Barbacid M . 1989 EMBO J. 8: 2283–2290

  • Katzav S, Sutherland M, Packham G, Yi T, Weiss A . 1994 J. Biol. Chem. 269: 32579–32585

  • Kawasaki Y, Senda T, Ishidate T, Koyama R, Morishita T, Iwayama Y, Higuchi O, Akiyama T . 2000 Science 289: 1194–1197

  • Miki T, Smith CL, Long JE, Eva A, Fleming TP . 1993 Nature 362: 462–465

  • Moores SL, Selfors LM, Fredericks J, Breit T, Fujikawa K, Alt FW, Brugge JS, Swat W . 2000 Mol. Cell. Biol. 20: 6364–6373

  • Movilla N, Bustelo XR . 1999 Mol. Cell. Biol. 19: 7870–7885

  • Osborne MA, Dalton S, Kochan JP . 1995 Biotechnology (NY) 13: 1474–1478

  • Ron D, Graziani G, Aaronson SA, Eva A . 1989 Oncogene 4: 1067–1072

  • Schuebel KE, Bustelo XR, Nielsen DA, Song BJ, Barbacid M, Goldman D, Lee IJ . 1996 Oncogene 13: 363–371

  • Schuebel KE, Movilla N, Rosa JL, Bustelo XR . 1998 EMBO J. 17: 6608–6621

  • Stradal T, Kranewitter W, Winder SJ, Gimona M . 1998 FEBS Lett. 431: 134–137

  • Takaki S, Sauer K, Iritani BM, Chien S, Ebihara Y, Tsuji K, Takatsu K, Perlmutter RM . 2000 Immunity 13: 599–609

  • Tedford K, Nitschke L, Girkontaite I, Charlesworth A, Chan G, Sakk V, Barbacid M, Fischer K-D . 2001 Nature Immunol. 2: 548–555

  • Van Aelst L, D'Souza-Schorey C . 1997 Genes Dev. 11: 2295–2322

  • Wakioka T, Sasaki A, Mitsui K, Yokouchi M, Inoue A, Komiya S, Yoshimura A . 1999 Leukemia 13: 760–767

  • Whitehead IP, Campbell S, Rossman KL, Der CJ . 1997 Biochim. Biophys. Acta 1332: F1–F23

  • Yokouchi M, Suzuki R, Masuhara M, Komiya S, Inoue A, Yoshimura A . 1997 Oncogene 15: 7–15

  • Yokouchi M, Wakioka T, Sakamoto H, Yasukawa H, Ohtsuka S, Sasaki A, Ohtsubo M, Valius M, Inoue A, Komiya S, Yoshimura A . 1999 Oncogene 18: 759–767

  • Zeng L, Sachdev P, Yan L, Chan JL, Trenkle T, McClelland M, Welsh J, Wang LH . 2000 Mol. Cell. Biol. 20: 9212–9224

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Acknowledgements

We thank Drs Tohru Tezuka and Tadashi Yamamoto for their gift of expression plasmid encoding Lck, Dr Takaya Satoh for the expression plasmid of proto-Dbl. This work was supported by Grants-in-Aid for Special Project Research on Cancer-Bioscience 12215024 from the Ministry of Education, Culture, Sports, Science, and Technology in Japan and for the program ‘Research for the Future’ of Japan Society for Promotion of Science

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  1. Division of Genetics, Institute of Medical Science, University of Tokyo, Shirokanedai 4-6-1 Minato, Tokyo, Japan

    Naoyuki Yabana & Masabumi Shibuya

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  1. Naoyuki Yabana
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  2. Masabumi Shibuya
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Correspondence to Masabumi Shibuya.

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Yabana, N., Shibuya, M. Adaptor protein APS binds the NH2-terminal autoinhibitory domain of guanine nucleotide exchange factor Vav3 and augments its activity. Oncogene 21, 7720–7729 (2002). https://doi.org/10.1038/sj.onc.1205927

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