PMID- 23620790 OWN - NLM STAT- MEDLINE DCOM- 20131111 LR - 20211021 IS - 1932-6203 (Electronic) IS - 1932-6203 (Linking) VI - 8 IP - 4 DP - 2013 TI - CBAP functions as a novel component in chemokine-induced ZAP70-mediated T-cell adhesion and migration. PG - e61761 LID - 10.1371/journal.pone.0061761 [doi] LID - e61761 AB - Activated chemokine receptor initiates inside-out signaling to transiently trigger activation of integrins, a process involving multiple components that have not been fully characterized. Here we report that GM-CSF/IL-3/IL-5 receptor common beta-chain-associated protein (CBAP) is required to optimize this inside-out signaling and activation of integrins. First, knockdown of CBAP expression in human Jurkat T cells caused attenuated CXC chemokine ligand-12 (CXCL12)-induced cell migration and integrin alpha4beta1- and alphaLbeta2-mediated cell adhesion in vitro, which could be rescued sufficiently upon expression of murine CBAP proteins. Freshly isolated CBAP-deficient primary T cells also exhibited diminution of chemotaxis toward CC chemokine ligand-21 (CCL21) and CXCL12, and these chemokines-induced T-cell adhesions in vitro. Adoptive transfer of isolated naive T cells demonstrated that CBAP deficiency significantly reduced lymph node homing ability in vivo. Finally, migration of T cell-receptor-activated T cells induced by inflammatory chemokines was also attenuated in CBAP-deficient cells. Further analyses revealed that CBAP constitutively associated with both integrin beta1 and ZAP70 and that CBAP is required for chemokine-induced initial binding of the talin-Vav1 complex to integrin beta1 and to facilitate subsequent ZAP70-mediated dissociation of the talin-Vav1 complex and Vav1 phosphorylation. Within such an integrin signaling complex, CBAP likely functions as an adaptor and ultimately leads to activation of both integrin alpha4beta1 and Rac1. Taken together, our data suggest that CBAP indeed can function as a novel signaling component within the ZAP70/Vav1/talin complex and plays an important role in regulating chemokine-promoted T-cell trafficking. FAU - Chiang, Yun-Jung AU - Chiang YJ AD - Institute of Microbiology and Immunology, National Yang-Ming University, Taipei, Taiwan. FAU - Ho, Kun-Chin AU - Ho KC FAU - Sun, Chien-Tsang AU - Sun CT FAU - Chiu, Jeng-Jiann AU - Chiu JJ FAU - Lee, Fang-Jen AU - Lee FJ FAU - Liao, Fang AU - Liao F FAU - Yang-Yen, Hsin-Fang AU - Yang-Yen HF FAU - Yen, Jeffrey Jong-Young AU - Yen JJ LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20130419 PL - United States TA - PLoS One JT - PloS one JID - 101285081 RN - 0 (Chemokines) RN - 0 (Integrin beta1) RN - 0 (Membrane Proteins) RN - 0 (Proto-Oncogene Proteins c-vav) RN - 0 (TMEM102 protein, human) RN - 0 (TMEM102 protein, mouse) RN - 0 (Talin) RN - 0 (VAV1 protein, human) RN - EC 2.7.10.2 (ZAP-70 Protein-Tyrosine Kinase) RN - EC 2.7.10.2 (ZAP70 protein, human) RN - EC 3.6.5.2 (rac1 GTP-Binding Protein) SB - IM MH - Animals MH - Cell Adhesion/drug effects MH - Cell Movement/*drug effects MH - Chemokines/*pharmacology MH - Chemotaxis/drug effects MH - Humans MH - Integrin beta1/metabolism MH - Jurkat Cells MH - Lymph Nodes/cytology/drug effects MH - Lymphocyte Activation/drug effects MH - Membrane Proteins/deficiency/*metabolism MH - Mice MH - Protein Binding/drug effects MH - Proto-Oncogene Proteins c-vav MH - Signal Transduction/drug effects MH - T-Lymphocytes/*cytology/drug effects/*metabolism MH - Talin/metabolism MH - ZAP-70 Protein-Tyrosine Kinase/*metabolism MH - rac1 GTP-Binding Protein/metabolism PMC - PMC3631140 COIS- Competing Interests: The authors have declared that no competing interests exist. EDAT- 2013/04/27 06:00 MHDA- 2013/11/12 06:00 PMCR- 2013/04/19 CRDT- 2013/04/27 06:00 PHST- 2013/01/02 00:00 [received] PHST- 2013/03/11 00:00 [accepted] PHST- 2013/04/27 06:00 [entrez] PHST- 2013/04/27 06:00 [pubmed] PHST- 2013/11/12 06:00 [medline] PHST- 2013/04/19 00:00 [pmc-release] AID - PONE-D-13-00685 [pii] AID - 10.1371/journal.pone.0061761 [doi] PST - epublish SO - PLoS One. 2013 Apr 19;8(4):e61761. doi: 10.1371/journal.pone.0061761. Print 2013.