FEBS Letters
Volume 584, Issue 15 , Pages 3279-3286, 4 August 2010

Abi1/Hssh3bp1 pY213 links Abl kinase signaling to p85 regulatory subunit of PI-3 kinase in regulation of macropinocytosis in LNCaP cells

Edited by Noboru Mizushima

  • Patrycja M. Dubielecka

      Affiliations

    • Laboratory of Cell Signaling, New York Blood Center, New York, NY 10065, USA
    • ,
  • Kazuya Machida

      Affiliations

    • Raymond and Beverly Sackler Laboratory of Genetics and Molecular Medicine, Department of Genetics and Developmental Biology, University of Connecticut Health Center, Farmington, CT 06030, USA
    • ,
  • Xiaoling Xiong

      Affiliations

    • Laboratory of Cell Signaling, New York Blood Center, New York, NY 10065, USA
    • ,
  • Sajjad Hossain

      Affiliations

    • Laboratory of Cell Signaling, New York Blood Center, New York, NY 10065, USA
    • ,
  • Mari Ogiue-Ikeda

      Affiliations

    • Raymond and Beverly Sackler Laboratory of Genetics and Molecular Medicine, Department of Genetics and Developmental Biology, University of Connecticut Health Center, Farmington, CT 06030, USA
    • ,
  • Ana C. Carrera

      Affiliations

    • Department of Immunology and Oncology, Centro Nacional de Biotecnologia, Consejo Superior de Investigaciones Cientificas, Carretera de Colmenar Km 15, Cantoblanco Madrid E-28049, Spain
    • ,
  • Bruce J. Mayer

      Affiliations

    • Raymond and Beverly Sackler Laboratory of Genetics and Molecular Medicine, Department of Genetics and Developmental Biology, University of Connecticut Health Center, Farmington, CT 06030, USA
    • ,
  • Leszek Kotula

      Affiliations

    • Laboratory of Cell Signaling, New York Blood Center, New York, NY 10065, USA
    • Corresponding Author InformationCorresponding author. Address: Laboratory of Cell Signaling, 310 E. 67th St., New York, NY 10065, USA. Fax: +1 212 570 3355.

Received 18 March 2010; received in revised form 9 June 2010; accepted 13 June 2010. published online 23 June 2010.

Abstract 

Macropinocytosis is regulated by Abl kinase via an unknown mechanism.We previously demonstrated that Abl kinase activity is, itself, regulated by Abi1 subsequent to Abl kinase phosphorylation of Abi1 tyrosine 213 (pY213) [1].Here we show that blocking phosphorylation of Y213 abrogated the ability of Abl to regulate macropinocytosis, implicating Abi1 pY213 as a key regulator of macropinocytosis.Results from screening the human SH2 domain library and mapping the interaction site between Abi1 and the p85 regulatory domain of PI-3 kinase, coupled with data from cells transfected with loss-of-function p85 mutants, support the hypothesis that macropinocytosis is regulated by interactions between Abi1 pY213 and the C-terminal SH2 domain of p85—thereby linking Abl kinase signaling to p85-dependent regulation of macropinocytosis.

Structured summary

MINT-7908602:Abi1 (uniprotkb:Q8IZP0) binds (MI:0407) to SHIP2 (uniprotkb:O15357) by array technology (MI:0008)

MINT-7908362:Abi1 (uniprotkb:Q8IZP0) binds (MI:0407) to Emt (uniprotkb:Q08881) by array technology (MI:0008)

MINT-7908235:Abi1 (uniprotkb:Q8IZP0) binds (MI:0407) to Lyn (uniprotkb:P07948) by array technology (MI:0008)

MINT-7908075:Abi1 (uniprotkb:Q8IZP0)binds(MI:0407) to Fgr (uniprotkb:P09769) by array technology (MI:0008)

MINT-7908330, MINT-7908522:Abi1 (uniprotkb:Q8IZP0) binds (MI:0407) to Vav1 (uniprotkb:P15498) by array technology (MI:0008)

MINT-7907962:Abi1 (uniprotkb:Q8IZP0) binds (MI:0407) to Fyn (uniprotkb:P06241) by array technology (MI:0008)

MINT-7908203:Abi1 (uniprotkb:Q8IZP0) binds (MI:0407) to Src(uniprotkb:P12931) by array technology (MI:0008)

MINT-7908570:Abi1 (uniprotkb:Q8IZP0) binds (MI:0407) to SHP-2 (uniprotkb:P35235) by array technology (MI:0008)

MINT-7908187, MINT-7908586:Abi1(uniprotkb:Q8IZP0) binds (MI:0407) to Gap (uniprotkb:P20936) by array technology (MI:0008)

MINT-7907981, MINT-7907995:Abi1 (uniprotkb:Q8IZP0) physically interacts (MI:0915) with p85a(uniprotkb:P26450) by anti tag coimmunoprecipitation (MI:0007)

MINT-7908251:Abi1 (uniprotkb:Q8IZP0) binds (MI:0407) to PLCG1 (uniprotkb:P19174) by array technology (MI:0008)

MINT-7908346:Abi1 (uniprotkb:Q8IZP0) binds (MI:0407) to Grb2 (uniprotkb:P62993) by array technology (MI:0008)

MINT-7907945:Abi1 (uniprotkb:Q8IZP0) binds (MI:0407) to Abl (uniprotkb:P00519) by array technology (MI:0008)

MINT-7908474:Abi1(uniprotkb:Q8IZP0)binds (MI:0407) to p85b (uniprotkb:O00459) by array technology (MI:0008)

MINT-7908107:Abi1 (uniprotkb:Q8IZP0) binds (MI:0407) to Hck (uniprotkb:P08631) by array technology (MI:0008)

MINT-7908011: p85a (uniprotkb:P26450) physically interacts (MI:0915) with Abi1 (uniprotkb:Q8IZP0) by pull down (MI:0096)

MINT-7908155:Abi1 (uniprotkb:Q8IZP0) binds (MI:0407) to FynT (uniprotkb:P06241-2) by array technology (MI:0008)

MINT-7908283, MINT-7908490:Abi1 (uniprotkb:Q8IZP0) binds (MI:0407) to p55g (uniprotkb:Q92569) by array technology (MI:0008)

MINT-7907929, MINT-7907815, MINT-7907832, MINT-7907865, MINT-7907897, MINT-7907913, MINT-7907881, MINT-7907848:Abi1 (uniprotkb:Q8IZP0) binds (MI:0407) to p85a (uniprotkb:P27986) by array technology (MI:0008)

MINT-7908059:Abi1 (uniprotkb:Q8IZP0) binds (MI:0407) to Frk (uniprotkb:P42685) by array technology (MI:0008)

MINT-7908378:Abi1(uniprotkb:Q8IZP0) binds (MI:0407) to CblC (uniprotkb:Q9ULV8) by array technology (MI:0008)

MINT-7908618:Abi1(uniprotkb:Q8IZP0) binds (MI:0407) to CblA (uniprotkb:B5MC15) by array technology (MI:0008)

MINT-7908139, MINT-7908538:Abi1 (uniprotkb:Q8IZP0) binds (MI:0407) to Nap4 (uniprotkb:O14512) by array technology (MI:0008)

MINT-7908426:Abi1 (uniprotkb:Q8IZP0) binds (MI:0407) to CblB (uniprotkb:Q13191) by array technology (MI:0008)

MINT-7908506:Abi1 (uniprotkb:Q8IZP0) binds (MI:0407) to Crk (uniprotkb:P46108) by array technology (MI:0008)

MINT-7908554:Abi1 (uniprotkb:Q8IZP0) binds (MI:0407) to mAbl (uniprotkb:P00520) by array technology (MI:0008)

MINT-7908043, MINT-7908394:Abi1 (uniprotkb:Q8IZP0) binds (MI:0407) to Vav2 (uniprotkb:P52735) by array technology (MI:0008)

MINT-7908458:Abi1 (uniprotkb:Q8IZP0) binds (MI:0407) to mSck/ShcB (uniprotkb:Q8BMC3) by array technology (MI:0008)

MINT-7908091:Abi1 (uniprotkb:Q8IZP0) binds (MI:0407) to Yes (uniprotkb:P07947) by array technology (MI:0008)

MINT-7908219:Abi1 (uniprotkb:Q8IZP0) binds (MI:0407) to Src (uniprotkb:P00523) by array technology (MI:0008)

MINT-7908123:Abi1 (uniprotkb:Q8IZP0) binds (MI:0407) to Fer (uniprotkb:P16591) by array technology (MI:0008)

MINT-7908410:Abi1(uniprotkb:Q8IZP0) binds (MI:0407) to CrkL (uniprotkb:P46109) by array technology (MI:0008)

MINT-7908314, MINT-7908442:Abi1 (uniprotkb:Q8IZP0) binds (MI:0407) to Arg (uniprotkb:P42684) by array technology (MI:0008)

MINT-7908299:Abi1 (uniprotkb:Q8IZP0) binds (MI:0407) to PLCG1 (uniprotkb:P10686) by array technology (MI:0008)

MINT-7908171:Abi1 (uniprotkb:Q8IZP0) binds (MI:0407) to Fes (uniprotkb:P07332) by array technology (MI:0008)

MINT-7908027:Abi1 (uniprotkb:Q8IZP0) binds (MI:0407) to Lck (uniprotkb:P06239) by array technology (MI:0008)

Keywords: Macropinocytosis, Abi1, Spectrin, p85, Tyr213

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PII: S0014-5793(10)00524-7

doi:10.1016/j.febslet.2010.06.029

FEBS Letters
Volume 584, Issue 15 , Pages 3279-3286, 4 August 2010

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