Silvia Bolland, Roger N Pearse, Tomohiro Kurosaki, Jeffrey V Ravetch 

Slides:



Advertisements
Similar presentations
CS1, a SLAM family receptor involved in immune regulation, is a therapeutic target in multiple myeloma  André Veillette, Huaijian Guo  Critical Reviews.
Advertisements

Volume 14, Issue 6, Pages (June 2001)
Volume 26, Issue 3, Pages (March 2007)
Volume 21, Issue 5, Pages (November 2004)
Volume 9, Issue 5, Pages (November 1998)
Regulation of FcεRI-mediated degranulation by an adaptor protein 3BP2 in rat basophilic leukemia RBL-2H3 cells by Kiyonao Sada, S. M. Shahjahan Miah, Koichiro.
by Koji Nakamura, Alexander Malykhin, and K. Mark Coggeshall
Vanessa L. Ott, PhD, Dana C. Fong, PhD, John C. Cambier, PhD 
Volume 129, Issue 2, Pages (August 2005)
Volume 118, Issue 4, Pages (April 2000)
Activation of the Erythropoietin Receptor Is Not Required for Internalization of Bound Erythropoietin by Diana L. Beckman, Lilie L. Lin, Mary E. Quinones,
SHIP Recruitment Attenuates FcγRIIB-Induced B Cell Apoptosis
Volume 7, Issue 2, Pages (August 1997)
Autoinhibition of c-Abl
by Mi-Ae Kang, Su-Young Yun, and Jonghwa Won
Volume 11, Issue 3, Pages (September 1999)
Volume 86, Issue 6, Pages (September 1996)
Volume 89, Issue 5, Pages (May 1997)
BLNK Immunity Volume 9, Issue 1, Pages (July 1998)
Neurexins Are Functional α-Latrotoxin Receptors
Volume 36, Issue 6, Pages (June 2012)
ASK1 Is Essential for JNK/SAPK Activation by TRAF2
Volume 4, Issue 4, Pages (April 1996)
Volume 15, Issue 6, Pages (December 2001)
Volume 4, Issue 1, Pages (January 1996)
Volume 9, Issue 5, Pages (November 1998)
A Tripartite Protein Complex with the Potential to Couple Synaptic Vesicle Exocytosis to Cell Adhesion in Brain  Stefan Butz, Masaya Okamoto, Thomas C.
Robert L.S Perry, Maura H Parker, Michael A Rudnicki  Molecular Cell 
BTK Regulates PtdIns-4,5-P2 Synthesis
Volume 7, Issue 1, Pages (July 1997)
MyD88: An Adapter That Recruits IRAK to the IL-1 Receptor Complex
Calnexin Controls the STAT3-Mediated Transcriptional Response to EGF
Volume 4, Issue 2, Pages (February 1996)
Manfred Kraus, Kaoru Saijo, Raul M Torres, Klaus Rajewsky  Immunity 
Volume 20, Issue 4, Pages (April 1998)
Role of the regulatory domain of the EGF-receptor cytoplasmic tail in selective binding of the clathrin-associated complex AP-2  Werner Boll, Andreas.
Naoko Kanda, Shinichi Watanabe  Journal of Investigative Dermatology 
Monica Kong-Beltran, Jennifer Stamos, Dineli Wickramasinghe 
SHIP Recruitment Attenuates FcγRIIB-Induced B Cell Apoptosis
Cyclooxygenase-2 Inhibitor Enhances Whereas Prostaglandin E2Inhibits the Production of Interferon-Induced Protein of 10 kDa in Epidermoid Carcinoma A431 
Volume 25, Issue 5, Pages (November 2006)
The Actin-Bundling Protein Palladin Is an Akt1-Specific Substrate that Regulates Breast Cancer Cell Migration  Y. Rebecca Chin, Alex Toker  Molecular.
Volume 9, Issue 3, Pages (March 2009)
Volume 36, Issue 6, Pages (June 2012)
Siqi Lin, Claudia Cicala, Andrew M Scharenberg, Jean-Pierre Kinet  Cell 
Volume 18, Issue 6, Pages (June 2003)
Volume 17, Issue 5, Pages (November 2002)
TRADD–TRAF2 and TRADD–FADD Interactions Define Two Distinct TNF Receptor 1 Signal Transduction Pathways  Hailing Hsu, Hong-Bing Shu, Ming-Gui Pan, David.
Volume 22, Issue 1, Pages 9-18 (January 2005)
Rsk1 mediates a MEK–MAP kinase cell survival signal
BLNK Required for Coupling Syk to PLCγ2 and Rac1-JNK in B Cells
Volume 8, Issue 14, Pages (July 1998)
Volume 7, Issue 2, Pages (August 1997)
SUMO-1 Modification Represses Sp3 Transcriptional Activation and Modulates Its Subnuclear Localization  Sarah Ross, Jennifer L Best, Leonard I Zon, Grace.
Jennifer Terrell, Susan Shih, Rebecca Dunn, Linda Hicke  Molecular Cell 
Silva H Hanissian, Raif S Geha  Immunity 
LAT Links the Pre-BCR to Calcium Signaling
Targeted Cleavage of Signaling Proteins by Caspase 3 Inhibits T Cell Receptor Signaling in Anergic T Cells  Irene Puga, Anjana Rao, Fernando Macian  Immunity 
Volume 13, Issue 1, Pages (July 2000)
Volume 9, Issue 5, Pages (November 1998)
RhoA GTPase Regulates B Cell Receptor Signaling
Volume 12, Issue 3, Pages (March 2000)
Volume 8, Issue 2, Pages (February 1998)
Volume 31, Issue 5, Pages (November 2009)
Volume 23, Issue 2, Pages (August 2005)
Elva Dı́az, Suzanne R Pfeffer  Cell 
A Smad Transcriptional Corepressor
Volume 12, Issue 6, Pages (March 2002)
The LIN-2/LIN-7/LIN-10 Complex Mediates Basolateral Membrane Localization of the C. elegans EGF Receptor LET-23 in Vulval Epithelial Cells  Susan M Kaech,
Volume 14, Issue 6, Pages (June 2001)
Presentation transcript:

SHIP Modulates Immune Receptor Responses by Regulating Membrane Association of Btk  Silvia Bolland, Roger N Pearse, Tomohiro Kurosaki, Jeffrey V Ravetch  Immunity  Volume 8, Issue 4, Pages 509-516 (April 1998) DOI: 10.1016/S1074-7613(00)80555-5

Figure 1 Schematic Representation of the Transfected Proteins FcγRII contains the complete sequence of murine FcγRIIB1, including an immunoreceptor tyrosine inhibitory motif (ITIM) in the cytoplasmic domain. Cyt. SHIP (cytoplasmic SHIP) is the complete murine SHIP protein, which contains an N-terminal SH2 domain, a 5′-phosphoinositol phosphatase domain (5′-IPase), two PTB binding site motifs (Y Y), and a proline-rich domain (Pro). Cyt. Btk (cytoplasmic Btk) is the complete human Btk protein, which includes SH1 (kinase), SH2, SH3, and an amino-terminal PH domain. Mem. SHIP (membrane SHIP) consists of the murine FcγRIIB1 extracellular and transmembrane domains (amino acids 1–305) fused to a murine SHIP protein that lacks the SH2 domain (amino acids 194–1187). Mem. Btk (membrane Btk) is composed of the extracellular domain of human CD16 (amino acids 1–212), the transmembrane domain of the human T cell receptor ζ chain (amino acids 30–58), and the complete sequence of human Btk in the cytoplasmic tail. Immunity 1998 8, 509-516DOI: (10.1016/S1074-7613(00)80555-5)

Figure 2 Membrane-Localized Btk Suppresses FcγRII Inhibition (A) Intracellular calcium2+ mobilization triggered by BCR-FcγRII coligation compared with BCR stimulation alone. The chicken BCR (surface IgM) was stimulated by cross-linking with an mAb (mouse IgM) against chicken IgM. For coligation of murine FcγRII with the BCR, rabbit antibody against mouse IgM was added prior to stimulation with the anti-chicken antibody. Arrows indicate the addition of anti-chicken IgM. DT40 cells were transfected with the murine FcγRII construct alone, or FcγRII together with the membrane Btk chimera or FcγRII together with the cytoplasmic Btk construct. Histograms show surface expression levels of transfected constructs as determined by FACS staining, where dotted lines indicate staining of untransfected cells. The calcium2+ traces shown are representative of at least two different independent clones and three different measurements for each case. (B) Expression level of endogenous and transfected Btk protein detected by immunoblotting with anti-Btk antibodies. Extracts from 5 × 104 cells were loaded. Lane 1 is DT40 transfected with FcγRII; lane 2 is DT40 transfected with FcγRII and membrane Btk; and lane 3 is DT40 transfected with FcγRII and cytoplasmic Btk. Immunity 1998 8, 509-516DOI: (10.1016/S1074-7613(00)80555-5)

Figure 3 Expression of Membrane-Localized Btk Suppresses SHIP Inhibition (A) Intracellular Ca2+ mobilization triggered by the BCR when coligated to membrane SHIP compared with BCR stimulation alone. DT40 cells were transfected with membrane SHIP together with the membrane Btk chimera or with the cytoplasmic Btk construct. Cells were stimulated as in Figure 2. (B) Expression level of endogenous and transfected Btk protein detected by immunoblot with anti-Btk antibodies. Lane 1 is an extract from DT40 cells transfected with membrane SHIP and membrane Btk; lane 2 is an extract from DT40 cells transfected with membrane SHIP and cytoplasmic Btk. Immunity 1998 8, 509-516DOI: (10.1016/S1074-7613(00)80555-5)

Figure 4 Membrane-Localized Btk Overcomes Wortmannin Inhibition Intracellular Ca2+ mobilization was measured after BCR engagement with anti-chicken IgM antibodies. Untransfected DT40 cells, cells transfected with the membrane Btk construct, or the cytoplasmic Btk construct were stimulated at the time point indicated (arrow). Dotted traces indicate that the stimulation was performed after 30 min incubation with 20 mM wortmannin. Immunity 1998 8, 509-516DOI: (10.1016/S1074-7613(00)80555-5)

Figure 5 Increased Membrane Localization of Endogenous Btk in DT40 ship−/− Cells (A) Wild-type DT40 and SHIP−/− DT40 cells were stimulated by cross-linking the BCR with anti-chicken IgM antibodies (+) or were left unstimulated (−). Cells were lysed in hypotonic buffer as described (Kawakami et al. 1994) 2 min after stimulation. Membrane fractions were analyzed by immunoblotting with anti-Btk. (B) Quantification of Btk enrichment in membrane fractions. The intensity of the Btk bands revealed in immunoblots of membrane fractions was measured by phosphorimager analysis (BioRad). The BCR expression level, detected on the same blot by incubation with anti-chicken IgM, was used to normalize values for the amount of membrane extract. Bars represent the average of four experiments in arbitrary units; standard errors are indicated. Immunity 1998 8, 509-516DOI: (10.1016/S1074-7613(00)80555-5)

Figure 6 Enhanced Ca2+ Mobilization in DT40 ship−/− Cells upon BCR Stimulation Intracellular Ca2+ mobilization was measured upon cross-linking of the BCR with anti-chicken IgM antibodies. Left, wild-type DT40 cells (ship+/+) were compared with SHIP−/− DT40 cells (ship−/−). Right, the response of SHIP−/− DT40 cells was compared with SHIP−/− DT40 cells transfected with membrane SHIP (mem.SHIP) or SHIP−/− DT40 cells preincubated for 30 min with 20 nM wortmannin (wort.). Immunity 1998 8, 509-516DOI: (10.1016/S1074-7613(00)80555-5)

Figure 7 Model for the Mechanism of Inhibition of Ca2+ Mobilization by SHIP Coligation of FcγRII to the BCR results in SHIP recruitment to the membrane via an SH2 domain interaction. Once in the membrane, SHIP hydrolyzes PI(3,4,5)P3 to PI(3,4)P2, thereby interfering with PH domain–mediated Btk membrane localization induced by BCR signaling. Membrane-localized Btk increases Ca2+ influx by an unknown mechanism. Additionally, SHIP can regulate BCR activating signals independent of FcγRII coligation by its phosphoinositol hydrolyzing activity, via interactions yet to be described. Immunity 1998 8, 509-516DOI: (10.1016/S1074-7613(00)80555-5)