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

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)