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Adhesion signaling by a novel mitotic substrate of src kinases

Oncogene volume 24, pages 5333–5343 (2005)Cite this article

Abstract

Src kinases are activated and relocalize to the cytoplasm during mitosis, but their mitotic function has remained elusive. We describe here a novel mitotic substrate of src kinases. Trask (transmembrane and associated with src kinases) is a 140 kDa type I transmembrane glycoprotein unrelated to currently known protein families. Src kinases phosphorylate Trask in vitro and mediate its mitotic hyperphosphorylation in vivo. Trask associates with both yes and src, is localized to the cell membrane during interphase, and undergoes cytoplasmic relocalization during mitosis. Overexpression of Trask leads to cell rounding and a loss of adhesion phenotype. Consistent with a function in cell adhesion, Trask interacts with a number of adhesion and matrix proteins including cadherins, syndecans, and the membrane-type serine protease 1 (MT-SP1), and is proteolytically cleaved by MT-SP1. Trask is unique among cell adhesion molecules in that it is under cell cycle regulation and thus links src kinases with the mitotic regulation of cell adhesion. This suggests a potential pathway by which hyperactive src kinases in tumors can deregulate adhesion signaling and mediate the metastatic phenotype.

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References

  • Bagrodia S, Chackalaparampil I, Kmiecik TE and Shalloway D . (1991). Nature, 349, 172–175.

  • Bagrodia S, Laudano AP and Shalloway D . (1994). J. Biol. Chem., 269, 10247–10251.

  • Bhatt AS, Takeuchi T, Ylstra B, Ginzinger D, Albertson D, Shuman MA and Craik CS . (2003). Biol. Chem., 384, 257–266.

  • Boyer B, Bourgeois Y and Poupon MF . (2002). Oncogene, 21, 2347–2356.

  • Brown TA, Yang TM, Zaitsevskaia T, Xia Y, Dunn CA, Sigle RO, Knudsen B and Carter WG . (2004). J. Biol. Chem., 279, 14772–14783.

  • Cartwright CA, Kamps MP, Meisler AI, Pipas JM and Eckhart W . (1989). J. Clin. Invest., 83, 2025–2033.

  • Chackalaparampil I and Shalloway D . (1988). Cell, 52, 801–810.

  • David-Pfeuty T and Nouvian-Dooghe Y . (1990). J. Cell Biol., 111, 3097–3116.

  • Erdjument-Bromage H, Lui M, Lacomis L, Grewal A, Annan RS, MacNulty DE, Carr SA and Tempst P . (1998). J. Chromatogr., 826, 167–181.

  • Erpel T and Courtneidge SA . (1995). Curr. Opin. Cell Biol., 7, 176–182.

  • Fumagalli S, Totty NF, Hsuan JJ and Courtneidge SA . (1994). Nature, 368, 871–874.

  • Geromanos S, Freckleton G and Tempst P . (2000). Anal. Chem., 72, 777–790.

  • Guy CT, Muthuswamy SK, Cardiff RD, Soriano P and Muller WJ . (1994). Genes Dev., 8, 23–32.

  • Hooper JD, Zijlstra A, Aimes RT, Liang H, Claassen GF, Tarin D, Testa JE and Quigley JP . (2003). Oncogene, 22, 1783–1794.

  • Irby RB and Yeatman TJ . (2000). Oncogene, 19, 5636–5642.

  • Irby RBM and Fujita DJJ . (1999). Nat. Genet., 21, 187–190.

  • Jones RJ, Avizienyte E, Wyke AW, Owens DW, Brunton VG and Frame MC . (2002). Br. J. Cancer, 87, 1128–1135.

  • Jove R and Hanafusa H . (1987). Annu. Rev. Cell Biol., 3, 31–56.

  • Kaplan KB, Swedlow JR, Varmus HE and Morgan DO . (1992). J. Cell Biol., 118, 321–333.

  • Kozak M . (1987). Nucleic Acids Res., 15, 8125–8148 (abstract).

  • Kraker AJ, Hartl BG, Amar A, Barvian MR, Showalter HD and Moore CW . (2000). Biochem. Pharmacol., 60, 885–898.

  • Lee SL, Dickson RB and Lin CY . (2000). J. Biol. Chem., 275, 36720–36725.

  • Lukong KE and Richard S . (2003). Biochim. Biophys. Acta, 1653, 73–86.

  • Mamidipudi V, Zhang J, Lee KC and Cartwright CA . (2004). Mol. Cell. Biol., 24, 6788–6798.

  • Mao W, Irby R, Coppola D, Fu L, Wloch M, Turner J, Yu H, Garcia R, Jove R and Yeatman TJ . (1997). Oncogene, 15, 3083–3090.

  • Mizenina OA and Moasser MM . (2004). Cell Cycle, 3, 796–803.

  • Moasser MM, Srethapakdi M, Sachar KS, Kraker AJ and Rosen N . (1999). Cancer Res., 59, 6145–6152.

  • Mustelin T and Hunter T . (2002). Science's STKE [Electronic Resource]: Signal Transduction Knowledge Environ., 115, PE3.

  • Ottenhoff-Kalff AE, Rijksen G, van Beurden EA, Hennipman A, Michels AA and Staal GE . (1992). Cancer Res., 52, 4773–4778.

  • Park J and Cartwright CA . (1995). Mol. Cell. Biol., 15, 2374–2382.

  • Park J, Meisler AI and Cartwright CA . (1993). Oncogene, 8, 2627–2635.

  • Pena SV, Melhem MF, Meisler AI and Cartwright CA . (1995). Gastroenterology, 108, 117–124.

  • Roche S, Fumagalli S and Courtneidge SA . (1995a). Science, 269, 1567–1569.

  • Roche S, Koegl M, Barone MV, Roussel MF and Courtneidge SA . (1995b). Mol. Cell. Biol., 15, 1102–1109.

  • Rosen N, Bolen JB, Schwartz AM, Cohen P, DeSeau V and Israel MA . (1986). J. Biol. Chem., 261, 13754–13759.

  • Santin AD, Zhan F, Bellone S, Palmieri M, Cane S, Bignotti E, Anfossi S, Gokden M, Dunn D, Roman JJ, O’Brien TJ, Tian E, Cannon MJ, Shaughnessy Jr J and Pecorelli S . (2004). Int. J. Cancer, 112, 14–25.

  • Scherl-Mostageer M, Sommergruber W, Abseher R, Hauptmann R, Ambros P and Schweifer N . (2001). Oncogene, 20, 4402–4408.

  • Sugimura M, Kobayashi K, Sagae S, Nishioka Y, Ishioka S, Terasawa K, Tokino T and Kudo R . (2000). Jpn. J. Cancer Res., 91, 395–398.

  • Takeuchi T, Harris JL, Huang W, Yan KW, Coughlin SR and Craik CS . (2000). J. Biol. Chem., 275, 26333–26342.

  • Tatsuka M, Ota T, Yamagishi N, Kashihara Y, Wada M, Matsuda N, Mitsui H, Seiki M and Odashima S . (1996). Mol. Carcinogen., 15, 300–308.

  • Taylor SJ, Anafi M, Pawson T and Shalloway D . (1995). J. Biol. Chem., 270, 10120–10124.

  • Taylor SJ and Shalloway D . (1994). Nature, 368, 867–871.

  • Wang LL, Richard S and Shaw AS . (1995). J. Biol. Chem., 270, 2010–2013.

  • Webster MA, Cardiff RD and Muller WJ . (1995). Proc. Natl. Acad. Sci. USA, 92, 7849–7853.

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Acknowledgements

We thank Lisa Denzin and Marilyn Resh for helpful discussions and Sami Mahrus and Chris Farady for reagents and helpful discussion regarding this manuscript. This work was supported by the American Cancer Society RSG-02-139-01-CDD (MMM) and NIH CA 72006 (CSC). ASB is supported by the NIH medical scientist training grant and a fellowship from the ARCS foundation.

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Authors and Affiliations

  1. School of Medicine, University of California, San Francisco, 94143, CA, USA

    Ami S Bhatt & Charles S Craik

  2. Program in Molecular Biology, Memorial Sloan-Kettering Cancer Center, Sloan-Kettering Institute, New York, 10021, NY, USA

    Hediye Erdjument-Bromage & Paul Tempst

  3. Department of Pharmaceutical Chemistry, University of California, San Francisco, 94143, CA, USA

    Charles S Craik

  4. Department of Medicine, University of California, San Francisco, 94143, CA, USA

    Mark M Moasser

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  1. Ami S Bhatt
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  2. Hediye Erdjument-Bromage
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  3. Paul Tempst
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  4. Charles S Craik
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  5. Mark M Moasser
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Corresponding author

Correspondence to Mark M Moasser.

Additional information

The Trask sequence has been deposited in the NCBI database with Genebank accession #AY167484

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Bhatt, A., Erdjument-Bromage, H., Tempst, P. et al. Adhesion signaling by a novel mitotic substrate of src kinases. Oncogene 24, 5333–5343 (2005). https://doi.org/10.1038/sj.onc.1208582

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