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Cloning and characterization of mPAL, a novel Shc SH2 domain-binding protein expressed in proliferating cells

Oncogene volume 18, pages 1867–1879 (1999)Cite this article

Abstract

Shc adaptor proteins play a role in linking activated cell surface receptors to the Ras signaling pathway in response to receptor mediated tyrosine kinase activation. While the function of Shc in the activation of the Ras pathway via binding to Grb2 has been well characterized, it is becoming increasingly apparent that Shc participates in additional signaling pathways through interactions with other cytoplasmic proteins. Using the yeast two-hybrid system, we have identified a unique Shc binding protein designated PAL (Protein expressed in Activated Lymphocytes) with no similarity to other known proteins. mPAL binds specifically to the Shc SH2 domain and unlike previously described Shc SH2 domain-protein interactions, the association of mPAL and Shc is phosphotyrosine-independent. Both mPAL RNA and protein expression are restricted to tissues containing actively dividing cells and proliferating cells in culture. mPAL expression is induced upon growth factor stimulation and is down-regulated upon growth inhibition. This pattern, and timing of mPAL expression and its association with the Shc adaptor molecule suggests a role for this protein in signaling pathways governing cell cycle progression.

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References

  • Anderson D, Koch CA, Grey L, Ellis C, Moran MF and Pawson T. . 1990 Science 250: 979–982.

  • Aronheim A, Engelberg D, Li N, Al-Alawi N, Schlessinger J and Karin M. . 1994 Cell 78: 949–961.

  • Bai C and Elledge SJ. . 1996 Methods Enzymol. 273: 331–347.

  • Baldari C, Pelicci G, Di Somma MM, Milia E, Giuli S, Pelicci PG and Telford JL. . 1995 Oncogene 16: 1141–1147.

  • Batzer LN, Daly R, Yajnik V, Skolnik E, Chardin P, Bar-Sagi D, Margolis B and Schlessinger J. . 1993 Nature 363: 85–88.

  • Blaikie P, Immanuel D, Wu D, Li N, Yajnik V and Margolis B. . 1994 J. Biol. Chem. 269: 23031–32034.

  • Bonfini L, Migliaccio E, Pelicci G, Lanfrancone L and Pelicci P. . 1996 TIBS 21: 257–261.

  • Buday L and Downward J. . 1993 Cell 73: 611–620.

  • Burns LA, Karnitz LM, Sutor SL and Abraham RT. . 1993 J. Biol. Chem. 268: 17659–17661.

  • Cazaubon SM, Ramos-Morales F, Fischer S, Schweighoffer F, Strosberg AD and Couraud PO. . 1994 J. Biol. Chem. 269: 24805–24809.

  • Chardin P, Camonis J, Gale WL, Van Aelst L, Schlessinger J, Wigler MH and Bar-sagi D. . 1993 Science 260: 1338–1343.

  • Charest A, Wagner J, Jacob S, McGlade CJ and Tremblay ML. . 1996 J. Biol. Chem. 272: 8424–8429.

  • Chen Y, Grall D, Salcini AE, Pelicci PG, Pouyssegur J and Van Obberghen-Schilling E. . 1996 EMBO J. 15: 1037–1044.

  • Cleghon V and Morrison DK. . 1994 J. Biol. Chem. 269: 17749–17755.

  • Crowe A, McGlade J, Pawson T and Hayman MJ. . 1994 Oncogene 9: 537–544.

  • Cutler RL, Liu L, Damen JE and Krystal G. . 1993 J. Biol. Chem. 268: 21463–21465.

  • Damen JE, Liu L, Rosten P, Humphries RK, Jefferson AB, Majerus PW and Krystal G. . 1996 Proc. Natl. Acad. Sci. USA 93: 1698–1693.

  • Damen JE, Liu L, Kutler RB and Krystal G. . 1993 Blood 82: 2296–2303.

  • Dikic I, Batzer AG, Blaikie P, Obermeier A, Ullrich A, Schlessinger J and Margolis B. . 1995 J. Biol. Chem. 270: 15125–15129.

  • Egan SE, Giddings BW, Brooks MW, Buday L, Sizeland AM and Weinberg RA. . 1993 Nature 363: 45–51.

  • Gotoh N, Muroya K, Hattori S, Nakamura S, Chida K and Shibuya M. . 1995 Oncogene 11: 2525–2533.

  • Gotoh N, Toyoda M and Shibuya M. . 1997 Mol. Cell. Biol. 17: 1824–1831.

  • Gotoh N, Tojo A and Shibuya M. . 1996 EMBO J. 15: 6197–6204.

  • Harmer SL and DeFranco AL. . 1997 Mol. Cell. Biol. 17: 4087–4095.

  • Jones-Villeneuve EMV, McBurney MW, Rogers KA and Kalnins VJ. . 1982 J. Cell. Biol. 94: 253–262.

  • Joung I, Strominger JL and Shin J. . 1996 Proc. Natl. Acad. Sci. USA 93: 5991–5995.

  • Kavanaugh WM, Pot DA, Chin SM, Deuter-Reinhard M, Jefferson AB, Norris FA, Masiarz FR, Cousens L, Majerus PW and Williams LT. . 1996 Curr. Biol. 6: 438–445.

  • Kozak M. . 1992 Annu. Rev. Cell. Biol. 8: 197–225.

  • Lee NH, Weinstock KG, Kirkless EF, Earle-Hughes JA, Fuldner RA, Marmaras S, Glodek A, Gocayne JD, Adams M, Kerlavage AR, Fraser CM and Venter JC. . 1995 Proc. Natl. Acad. Sci. USA 92: 8303–8307.

  • Lehmann JM, Riethmuller G and Johnson JP. . 1990 Nucl. Acids. Res. 18: 1048.

  • Lioubin MN, Algate PA, Tsai S, Carlberg K, Aebersold R and Rohrschneider LR. . 1996 Genes Dev. 10: 1084–1095.

  • Liu SK and McGlade CJ. . 1998 Oncogene in press.

  • Lorenzo MJ, Gish GD, Houghton C, Stonehouse TJ, Pawson T, Ponder BA and Smith DP. . 1997 Oncogene 14: 763–771.

  • Malek SN and Desiderio S. . 1994 J. Biol. Chem. 269: 33009–33020.

  • Maniero F, Pepe A, Wary KK, Spinardi L, Mohammadi M, Schlessinger J and Giancotti FG. . 1995 EMBO J. 14: 4470–4481.

  • Marengere LEM, Mirtsos C, Kozieradzki I, Veillette A, Mak TW and Penninger JM. . 1997 J. Immunol. 159: 70–76.

  • Marengere LEM, Waterhouse P, Duncan GS, Mittrucker H-W, Feng G-S and Mak TW. . 1996 Science 272: 1170–1173.

  • Margolis B, Hu P, Katzav S, Li W, Oliver JM, Ullrich A, Weiss A and Schlessinger J. . 1992 Nature 356: 71–74.

  • Matoskova B, Wong TW, Salcini Ae, Pelicci PG and Difiore PP. . 1995 Mol. Cell. Biol. 15: 3805–3812.

  • McBurney MW. . 1993 Int. J. Dev. Biol. 37: 135–140.

  • McBurney MW, Jones-Villeneuve EMV, Edwards MKS and Anderson PJ. . 1982 Nature 299: 165–167.

  • McBurney MW, Rheul KR, Ally AI, Nasipuri S, Bell JC and Craig J. . 1988 J. Neurosci. 8: 1063–1073.

  • McGlade J, Cheng A, Pelicci G, Pelicci PG and Pawson T. . 1992a) Proc. Natl. Acad. Sci. USA 89: 8869–8873.

  • McGlade CJ, Ellis C, Reedijk M, Anderson D, Mbamalu G, Reith AD, Panayotou G, End P, Bernstein A, Kazlauskas A, Waterfield MD and Pawson T. . 1992b Mol. Cell. Biol. 12: 991–997.

  • Migliaccio E, Mele S, Salcini AE, Pelicci G, Lai K, Superti-Furga G, Pawson T, Di Fiore PP, Lanfrancone L and Pelicci PG. . 1997 EMBO J. 16: 706–716.

  • Nantel A, Mohammed-Ali K, Sherk J, Posner BI and Thomas DY. . 1998 J. Biol. Chem. 273: 10473–10484.

  • O'Bryan JP, Lambert QT and Der Cj. . 1998 J. Biol. Chem. 273: 20431–20437.

  • Obermeier A, Bradshaw BA, Seedorf K, Choidas A, Schlessinger J and Ullrich A. . 1994 EMBO J. 13: 1585–1590.

  • Pawson T. . 1995 Nature 373: 573–579.

  • Pelicci G, Lanfrancone L, Salcini AE, Romano A, Mele S, borrello MG, Segatto O, Di Fiore PP and Pelicci PG. . 1995a Oncogene 11: 899–907.

  • Pelicci G, Lanfrancone L, Grigani F, McGlade J, Cavallo F, forni G, Nicoletti I, Grignani F, Pawson T and Pelicci PG. . 1992 Cell 70: 93–104.

  • Pelicci G, Giordano S, Zhen Z, Salcini AE, Lanfrancone L, Bardelli A, Panayotou G, Waterfield MD, Ponzetto C, Pelicci PG and Comoglio PM. . 1995b Oncogene 10: 1631–1638.

  • Pendergast AM, Muller AJ, Havlik MH, Maru Y and Witte ON. . 1991 Cell 66: 161–171.

  • Pronk GJ, McGlade J, Pelicci G, Pawson T and Bos LJ. . 1993 J. Biol. Chem. 268: 5748–5753.

  • Ptaznik A, Traynor-Kaplan A and Bokoch GM. . 1995 J. Biol. Chem. 270: 19969–19973.

  • Raffel GD, Parmar K and Rosenberg N. . 1996 J. Biol. Chem. 271: 4640–4645.

  • Ravichandran KS, Lee K, Songyang Z, Cantley LC, Burn P and Burakoff SJ. . 1993 Science 262: 902–905.

  • Ravichandran KS and Burakoff SJ. . 1994 J. Biol. Chem. 269: 1599–1602.

  • Ravichandran KS, Igras V, Shoelson SE, Fesik SW and Burakoff SJ. . 1996 Proc. Natl. Acad. Sci. USA 28: 5275–5280.

  • Ricketts WA, Rose DW, Shoelson S and Olefsky JM. . 1996 J. Biol. Chem. 271: 26165–26169.

  • Roche S, McGlade J, Jones M, Gish GD, Pawson T and Courtneidge SA. . 1996 EMBO J. 15: 4940–4946.

  • Rozakis-Adcock M, McGlade J, Mbamalu G, Pelicci G, Daly R, Li W, Batzer A, Thomas S, Brugge J, Pelicci PG and Pawson T. . 1992 Nature 360: 689–692.

  • Rozakis-Adcock M, Fernley R, Wade J, Pawson T and Bowtell D. . 1993 Nature 363: 83–85.

  • Rudnicki MA, Sawtell NM, Rheul KR, Berg R, Craig JC and McBurney MW. . 1990 J. Cell Physiol. 142: 89–98.

  • Salcini AE, McGlade J, Pelicci G, Nicoletti I, Pawson T and Pelicci PG. . 1994 Oncogene 9: 2827–2836.

  • Sambrook J, Fritsch EF and Maniatis T. . 1989 Molecular Cloning: A Laboratory Manual. Second Edition. Cold Spring Harbor Laboratory Press: Cold Spring Harbor, NY.

    Google Scholar 

  • Saxton TM, van Oostveen I, Bowtell D, Aebersold R and Gold MR. . 1994 J. Immunol. 153: 623–636.

  • Segatto O, Pelicci G, Giuli S, Digiesi G, Di Fiore PP, McGlade J, Pawson T and Pelicci PG. . 1993 Oncogene 9: 2105–2112.

  • Songyang Z, Margolis B, Chaudhuri M, Shoelson SE and Cantley LC. . 1995 J. Biol. Chem. 270: 14863–14866.

  • Songyang Z, Shoelson SE, McGlade J, Olivier P, Pawson T, Bustelo XR, Barbacid M, Save H, Hanafusa H, Yi T, Ren R, Baltimore D, Ratnofsky S, Feldman RA and Cantley LC. . 1994 Mol. Cell. Biol. 14: 2777–2785.

  • Touhara K, Hawes BE, van Biesen T and Lefkowitz RJ. . 1995 Proc. Natl. Acad. Sci. USA 92: 9284–9287.

  • Vadlamudi RK, Young I, Strominger JL and Shin J. . 1996 J. Biol. Chem. 271: 20235–20237.

  • van Biesen T, Hawes BE, Luttrell DK, Krueger KM, Touhara K, Porfiri E, Sakaue M, Luttrell LM and Lefkowitz RJ. . 1995 Nature 376: 781–784.

  • van der Geer P, Hunter T and Lindberg RA. . 1994 Annu. Rev. Cell. Biol. 10: 251–337.

  • van der Geer P, Wiley S, Lai VK-M, Olivier JP, Gish GD, Stephens R, Kaplan D, Shoelson S and Pawson T. . 1995 Curr. Biol. 5: 404–412.

  • van der Geer P, Wiley S, Gish GD and Pawson T. . 1996 Curr. Biol. 6: 1435–1444.

  • Wary KK, Mainiero F, Isakoff SJ, Marcantonio EE and Giancotti FG. . 1996 Cell 87: 733–743.

  • Waterhouse P, Penninger JM, Timms E, Wakeham A, Shahinian A, Lee KP, Thompson CB, Griesser H and Mak TW. . 1995 Science 270: 985–988.

  • Yokote K, Mori S, Hansen K, McGlade J, Pawson T. Heldin CH and Claesson-Welsch L. . 1994 J. Biol. Chem. 269: 15337–15343.

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Acknowledgements

Rosemarie Schmandt and Stanley Liu contributed equally to the data presented in this paper. We thank Sascha Dho, Sara Jacob, Cheryl Wolting and Stacy Woods for technical assistance, David Grosshans for DNA sequencing, Andrew Hessel and Mike Bass for assistance with sequence analysis, Luc Marengere for the activated T-cell lysates, Denis Bouchard for assistance with FACS analysis, Marynette Rihaynek and the peptide synthesis group at AMGEN Boulder for antibody preparation and Tony Pawson, Ben Margolis, and Mike Moran for GST-fusion protein constructs. We also thank Dwayne Barber, Dan Dumont and Michelle French for critical reading of the manuscript. This work was supported by Amgen and operating funds from the Medical Research Council of Canada. RS is supported by an MRC postdoctoral fellowship.

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  1. C Jane McGlade

    Present address: Department of Medical Biophysics, University of Toronto, 620 University Avenue, Suite 706, Toronto, Ontario, Canada, M5G 2C1

  2. C Jane McGlade

    Present address: The Arthur and Sonia Labatt Brain Tumour Research Centre, The Hospital for Sick Children, 555 University Avenue, Toronto, Ontario, Canada, M5G 1X8

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  1. Ontario Cancer Institute, University of Toronto, 620 University Avenue, Suite 706, Toronto, Ontario, M5G 2C1, Canada

    Rosemarie Schmandt, Stanley K Liu & C Jane McGlade

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Schmandt, R., Liu, S. & McGlade, C. Cloning and characterization of mPAL, a novel Shc SH2 domain-binding protein expressed in proliferating cells. Oncogene 18, 1867–1879 (1999). https://doi.org/10.1038/sj.onc.1202507

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