Supplementary information S1 (table): Specifications of individual protein protein interactions within the Cbl and Cbl-b interactomes

Size: px

Start display at page:

Download "Supplementary information S1 (table): Specifications of individual protein protein interactions within the Cbl and Cbl-b interactomes"

Jonathan Reynolds
5 years ago
Views:

1 Supplementary information S1 (table): Specifications of individual protein protein interactions within the Cbl and Cbl-b interactomes Cbl/Cbl-b binding protein Cbl domain/residue Binding protein domain/residue Indirect (via) Ligand dependency Detection method β, τ, ζ RSxSxP; ps619 + ps623, ps639 + ps C-terminal residues TCR/CD3 engagement, PMA Y2H, IP, GST 3BP2 C-terminal ptyr SH2 TCR/CD3 engagement, PMA GST Abl C-terminal ptyr SH2 TCR/CD3, BCR engagement IP, GST Abl Proline-rich SH3 Constitutive IP Actin Multiple pathways Constitutive and induced IP, GST, IF AIP4/Itch Proline-rich WW Constitutive Y2H, IP APS TKB py618 PDGF IP, APS phosphopeptide pulldown PubMed ID ArgBP2 Proline-rich SH3 B&C Constitutive Y2H, IP B-cell receptor BCR engagement IP, IF BCR Abl ptyr SH2 Y2H, IP Bim?? M-CSF IP, GST, IF Blk C-terminal ptyr SH2 TCR/CD3, BCR engagement IP, GST BLNK TKB py115 BCR engagement GST, far western Bsh??? Y2H Btk Proline-rich ( ) SH3 BCR engagement GST, NMR

2 CAP Proline-rich SH3 C-terminal part of domain Constitutive Y2H, IP, GST Cbl/Cbl-b LZ LZ Constitutive Y2H, IP CD02 CD2AP Inducible IB CD05 TKB DNEpY motif Pervanadate-treated thymocytes IP CD09 Antibody engagement IB CD116 (GM-CSFR) GM-CSF IB CD16 Antibody engagement IB CD19?? p85? IP CD26 IB CD28 integrins? Anti-CD28 receptor antibody IB CD38 Anti-CD38 receptor antibody IB CD40 CD40L IP CD43 Inducible IB CIN85/SETA/RUK C-terminal PXXXPR SH3 A&B&C EGF Y2H, IP, GST CD2AP/CMS C-terminal PXXXPR SH3 A&B&C EGF Y2H, IP, GST c-kit?? Grb2 SCF IP, GST c-met/hgfr TKB py1003 HGF IP

3 c-mp1 (Thrombopoietin R) Grb2 TPO IB Cool-1/βPix C-terminal PXXXPR SH3 Constitutive IP, GST Cool-2/αPix Proline-rich SH3 Constitutive Y2H, IP Crk py700/774 SH2 TCR/CD3 engagement IP, GST CrkII py700/774 SH2 TCR/CD3 engagement IP, GST CrkL Proline-rich SH3 Constitutive GST CrkL py700/774 SH2 TCR/CD3 engagement IP, GST, Far Western CSF1R TKB py-973 CSF IP Csk Indirect IP Cytokeratin 18 Proline-rich ( )?? Y2H Dap160/Intersectin Proline-rich SH3 Ligand dependent Y2H Dynamin Dab160 SH3s A D Ligand dependent IP EGFR TKB py1045 EGF IP Endophilin 1 Proline-rich ( ) SH3 ( )? Spot peptide array screen Endophilin A3 CIN85 Inducible IP, GST, IF

4 EphA2 TKB EphA1 IP, GST EphA3 TKB EphA1 IP EphB4?? EphB2 IP EphB6 TKB? EphB1 IP EpoR APS Epo IB ErbB2 TKB py1112 Ligand dependent IP, IF, GST Ewg??? Y2H FAK Src IP, IF Fas Anti-Fas receptor antibody IB Fcε RI SLP76, Grb2, Shc Antibody engagement IB Fcγ RI, RII, RIII SLP76, Grb2, Shc Antibody engagement IB FGFR 1 3 Grb2 py306 FRS2 FGF IP Fgr C-terminal ptyr SH2 Fibronectin-induced cell adhesion IP Fgr Proline-rich SH3 Constitutive IP Flk-1 TKB VEGF IP Flotillin 1 CAP IP Flt-1 TKB? VEGF IP Flt3 receptor TKB DNEY Flt3 ligand IB FRS2 Proline-rich? Grb2 FGF IP, GST Fyn Proline-rich ( ) SH3 Constitutive IP, GST Fyn/FynT C-term ptyr SH2 TCR/CD3, BCR engagement IP, GST Grb2 Proline-rich ( ) SH3 N-terminal Constitutive IP, GST

5 Hck Proline-rich SH3 Constitutive IP, GST Hck C-terminal ptyr SH2 Induced GST, Far Wstern ICAM-1 cbl-b / mice IL-2R IL-2 IB IL-3R IL-3 IB IL-4R IL-4 IB IL-7R IL-7 IB Insulin receptor APS + CAP Insulin IP, GST, IF Integrins α ΙΙβ, α 4, α V, α 7, α Μ, β 1, β 2, β 3 Multiple pathways Induced IP, IF IRS-1/IRS-2 Insulin IRS-1/IRS-2 knockout mice Itk/Tsk Proline-rich PPPPXXR SH3 Constitutive GST Jak2 Grb2 or APS TPO IP Lck Proline-rich SH3 Cnstitutive GST Lck C-terminal ptyr SH2 TCR/CD3 engagement GST LRIG1 N-terminal half juxtamembrane EGF IP, GST L-selectin Inducible in lymphocytes IB Lyn Proline-rich SH3 Constitutive Y2H, IP, GST Lyn C-terminal ptyr SH2 Induced Y2H Lyp1 TKB Putative PXXpY Constitutive IP

6 Myosin IC Proline-rich ( ) SH3 Y2H Nck Proline-rich SH3 A&B Constitutive IP, Far Western Nedd4 Proline-rich WW Constitutive GST, IP NGFR p75ntr TKB C terminus NGF Y2H, GST Notch1? Intracellular? IP, GST NTAL?? CD3, BCR, Fcγ and Fcε receptor engagement p85α, β Proline-rich SH3 Constitutive GST p85α, β py731 SH2 TCR/CD3, BCR engagement IP, GST Paxillin? N-terminus? Constitutive IP, GST PDGFRα, β TKB py residues DNLY, DNAY (a) DNDY(b) APS (py1021) PDGF IP PKCα /θ C terminus? Constitutive IP, GST PLCγ 1/2 proline rich SH3 Constitutive GST PLCγ 1/2 ptyr Cbl SH2 C-terminal Inducible IP Y2H, IP Prolactin receptor Prolactin IB Pyk2 Src Integrin-inducible IP, IF RNF ? Y2H Ron RTK TKB py py1353 Grb2 py1360 MSP IP, IF Sam68 SFKs Constitutive IP SH3P17 Proline-rich ( ) SH3 Y2H SH3P2 proline rich SH3 Constitutive Y2H, IP SHC Grb2 Induced IP

7 SHIP2?? CAP Constitutive Y2H, IP, GST SHP1 py774 SH2 N-terminal IP SHP2 py Cbl SH2 N-terminal SLP-76 IP, GST SLAP/SLAP2 N terminus (25 351) SLAP: C-terminal hydrophobic region; SLAP2: last C-terminal 70 residues; SLAP2- V does not bind Constitutive SLP76 C terminal/py Cbl Constitutive/FcγRI inducible IP Y2H, IP, GST Sprouty 2 TKB, RING py55 Upon Sprouty 2 induction by ligand Y2H, IP, GST Src TKB py416 Src activation IP Src Proline-rich SH3 Constitutive IP, GST Src C-terminal ptyr SH2 Induced IP, GST Src-viral Proline-rich SH3 Constitutive IP Sts1/Sts2 Proline-rich SH3 Constitutive Y2H, IP Syk TKB py323 TCR/CD3, BCR engagement Y2H, IP, GST, Far Western Syk Proline-rich py317 tubulin Constitutive IP Synapsin I Synaptojanin Dab160 SH3s A B Dab160 SH3s A D Induced IP Talin??? Constitutive IP T-cell receptor TCR/CD3 engagement IP, IF, GST TNFR?? TNFα IB Induced IP TRANCE-R SFKs TRANCE IP

8 Tubulin?? CIN85 Alix or Syk or Vav Constitutive IP, IF, colchicine agarose pulldown TULA Proline-rich SH3 Constitutive IP Tyk2 Proline-rich Constitutive IP Tyk2 IFNα IP Type 1 INFR IFNα, β IB Type 2 INFR IFNγ IB UBC4 RING? Constitutive in vitro UBcH5B/C RING? Constitutive in vitro UbcH7 RING L1 and L2 loops and H1 helix Constitutive Y2H, IP, GST ubiquitin UBA of Cbl-b Hydrophobic patch Constitutive GST Vav1/Vav2 py700 SH2 TCR/CD3 engagement IP, GST, Far Western VCAM-1 Anti-VCAM-1 antibodies IB ZAP-70 TKB py292 TCR/CD3, BCR engagement IP, GST This table characterizes individual interactions of the Cbl/Cbl-b interactome. The first column (Cbl/Cbl-b binding protein) outlines the proteins that have been described to undergo an interaction with Cbl or Cbl-b. The second column (Cbl domain/residue) outlines where the interaction takes place within the Cbl molecule. Please note that this panel exclusively applies to the Cbl molecule, not to Cbl-b. In the case of a direct interaction, the third column (Binding protein domain/residue) identifies the Cbl-binding site within the target molecule. If the interaction is indirect, the protein that mediates the interaction is identified in the fourth column (Indirect (via)). The fifth column (Ligand dependency) describes whether an interaction is constitutive or if it is triggered by a certain stimulus. It also names the stimulus necessary to induce the interaction. The sixth column (Detection method) lists the techniques used to identify a certain interaction, and the last panel (PubMed ID) gives a limited overview on the literature used to compile this dataset. Copying and pasting the ID into PubMed ( directs the reader to the corresponding abstract of the cited article. Please note that the list can only reflect the current knowledge about the Cbl/Cbl-b interactomes. For an updated version of the interactomes please follow the Cbl and

9 Cbl-b interactome links given in the main body of the manuscript. It will take you to the Cbl and Cbl-b interactomes at The Grid, which are permanently under revision. The Osprey program will enable readers to create a more update version of the interactomes there. Acronyms: 3BP2, c-abl-sh3-domain-binding protein-2; AIP4, atrophin-1-interacting protein-4; APS, adaptor protein with pleckstrin homology and SH2 domains; ArgBP2, Arg/Ablbinding protein-2; BCR, B-cell receptor; BLNK, B-cell linker; CAP, c-cbl-associated protein; CD2AP, CD2-associated protein; CMS, Cas ligand with multiple SH3 domains; CrkL, Crk ligand; CSF, colony-stimulating factor; CSF-1R, CSF-1 receptor; EGF, epidermal growth factor receptor; EGFR, EGF receptor; Epo, erythropoietin; EpoR, Epo receptor; FAK, focal adhesion kinase; FGF, fibroblast growth factor receptor; FGFR, FGF receptor; FRS2, FGFR substrate-2; Grb2, growth-factor-receptorbound-2; GM-CSFR, granulocyte-macrophage CSF receptor; GST, glutathione-s-transferase pulldown; HGF, hepatocyte growth factor; HGFR, HGF receptor; IB, immunoblotting; ICAM-1, intercellular adhesion molecule-1; IF, immunofluorescence; IL, interleukin; IL-R, IL receptor; IFN, interferon; IFNR, IFN receptor; IP, immunoprecipitation; IRS, insulin receptor substrate; Itk, IL-2-inducible T-cell kinase; Jak, Janus kinase; LRIG1, leucine-rich repeats and immunoglobulin-like domains protein-1; LZ, leucine zipper; M-CSF, macrophage CSF; MSP, macrophage-stimulating protein; NGF, nerve growth factor receptor; NGFR, NGF receptor; NMR, nuclear magnetic resonance; NTAL, non-t-cell activation linker; NTR; neurotrophin; PDGF, platelet-derived growth factor; PDGFR, PDGF receptor; PKC, protein kinase C; PLC, phospholipase C; Pix (p21-activated kinase (PAK)-interacting exchange factor; PMA; phorbol 12-myristate 13-acetate; RTK, receptor tyrosine kinase; SCF, stem-cell factor; SETA, SH3 domain-containing gene expressed in tumorigenic astrocytes; SH2, Src-homology-2; SH3, Src-homology-3; SHC, SH2-domain-containing; SFKs, Src-family kinases; SHIP, SH2-containing inositol phosphatase; SHP, SH2-containing phosphatase; SLAP, Src-like adaptor protein; SLP-76, SH2-domain-containing leukocyte protein of 76 kda; TCR, T-cell receptor; TKB, tyrosine kinase-binding; TNF, tumour necrosis factor; TNFR, TNF receptor; TPO, thrombopoietin; TRANCE, TNF-related activation-induced cytokine ; TRANCE-R, TRANCE receptor; Tsk, T-cell-specific kinase; TULA, T cell ubiquitin ligand; UBA, ubiquitin-associated; UBC, ubiquitinconjugating; VCAM, vascular cell adhesion molecule; VEGF, vascular endothelial growth factor; WW, domain with two conserved tryptophan (W) residues; Y2H, yeast two-hybrid; ZAP70, zeta-associated protein of 70 kda.

Signaling Through Immune System Receptors (Ch. 7)

Signaling Through Immune System Receptors (Ch. 7) 1. General principles of signal transduction and propagation. 2. Antigen receptor signaling and lymphocyte activation. 3. Other receptors and signaling