Mechanism of recruitment of WASP to the immunological synapse and of its activation following TCR ligation

被引：223

作者：

Sasahara, Y

Rachid, R

Byrne, MJ

de la Fuente, MA

Abraham, RT

Ramesh, N ^{[1
]}

Geha, RS

机构：

[1] Childrens Hosp, Div Immunol, Boston, MA 02115 USA

[2] Harvard Univ, Sch Med, Dept Pediat, Boston, MA 02115 USA

[3] Duke Univ, Med Ctr, Dept Pharmacol, Durham, NC 27710 USA

来源：

MOLECULAR CELL | 2002年 / 10卷 / 06期

关键词：

D O I：

10.1016/S1097-2765(02)00728-1

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

F-actin polymerization following engagement of the T cell receptor (TCR) is dependent on WASP and is critical for T cell activation. The link between TCR and WASP is not fully understood. In resting cells, WASP exists in a complex with WIP, which inhibits its activation by Cdc42. We show that the adaptor protein CrkL binds directly to WIP. Further, TCR ligation results in the formation of a ZAP-70-CrkL-WIP-WASP complex, which is recruited to lipid rafts and the immunological synapse. TCR engagement also causes PKCtheta-dependent phosphorylation of WIP, causing the disengagement of WASP from the WIP-WASP complex, thereby releasing it from WIP inhibition. These results suggest that the ZAP-70-CrkL-WIP pathway and PKCtheta link TCR to WASP activation.

引用

收藏

页码：1269 / 1281

页数：13

相关论文

共 43 条

[1] Understanding the molecular basis of Wiskott-Aldrich syndrome [J].

Abo, A .

CELLULAR AND MOLECULAR LIFE SCIENCES, 1998, 54 (10) :1145-1153

[2] Mutant T cell lines as model systems for the dissection of T cell antigen receptor signaling pathways [J].

Abraham, RT .

IMMUNOLOGIC RESEARCH, 2000, 22 (2-3) :95-117

[3] The Wiskott-Aldrich syndrome protein-interacting protein (WIP) binds to the adaptor protein Nck [J].

Anton, IM ;

Lu, WG ;

Mayer, BJ ;

Ramesh, N ;

Geha, RS .

JOURNAL OF BIOLOGICAL CHEMISTRY, 1998, 273 (33) :20992-20995

[4] WIP deficiency reveals a differential role for WIP and the actin cytoskeleton in T and B cell activation [J].

Antón, IM ;

de la Fuente, MA ;

Sims, TN ;

Freeman, S ;

Ramesh, N ;

Hartwig, JH ;

Dustin, ML ;

Geha, RS .

IMMUNITY, 2002, 16 (02) :193-204

[5] The Src homology 2 domain of Vav is required for its compartmentation to the plasma membrane and activation of C-jun NH2-terminal kinase 1 [J].

Arudchandran, R ;

Brown, MJ ;

Peirce, MJ ;

Song, JS ;

Zhang, JA ;

Siraganian, RP ;

Blank, U ;

Rivera, J .

JOURNAL OF EXPERIMENTAL MEDICINE, 2000, 191 (01) :47-59

[6] Membrane lipid microdomains and the role of PKCθ in T cell activation [J].

Bi, K ;

Altman, A .

SEMINARS IN IMMUNOLOGY, 2001, 13 (02) :139-146

[7] The immunological synapse [J].

Bromley, SK ;

Burack, WR ;

Johnson, KG ;

Somersalo, K ;

Sims, TN ;

Sumen, C ;

Davis, MM ;

Shaw, AS ;

Allen, PM ;

Dustin, ML .

ANNUAL REVIEW OF IMMUNOLOGY, 2001, 19 :375-396

[8] WASP recruitment to the T cell:APC contact site occurs independently of Cdc42 activation [J].

Cannon, JL ;

Labno, CM ;

Bosco, G ;

Seth, A ;

McGavin, MHK ;

Siminovitch, KA ;

Rosen, MK ;

Burkhardt, JK .

IMMUNITY, 2001, 15 (02) :249-259

[9] ZAP-70 - A 70 KD PROTEIN-TYROSINE KINASE THAT ASSOCIATES WITH THE TCR ZETA-CHAIN [J].

CHAN, AC ;

IWASHIMA, M ;

TURCK, CW ;

WEISS, A .

CELL, 1992, 71 (04) :649-662

[10] ISOLATION OF A NOVEL GENE MUTATED IN WISKOTT-ALDRICH SYNDROME [J].

DERRY, JMJ ;

OCHS, HD ;

FRANCKE, U .

CELL, 1994, 78 (04) :635-644

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