title: Vav1 increases Bcl-2 expression by selective activation of Rac2-Akt in leukemia T cells.
abstract: Vav proteins are guanine nucleotide exchange factors (GEFs) that activate a group of small G proteins (GTPases). Vav1 is predominantly expressed in hematopoietic cells, whereas Vav2 and Vav3 are ubiquitously distributed in almost all human tissues. All three Vav proteins contain conserved structural motifs and associate with a variety of cellular activities including proliferation, migration, and survival. Previous observation with Jurkat leukemia T cells showed that Vav1 possessed anti-apoptotic activity by enhancing Bcl-2 transcription. However the mechanism has not been unveiled. Here, we explored the effectors of Vav1 in promoting Bcl-2 expression in Jurkat cells and revealed that Rac2-Akt was specifically evoked by the expression of Vav1, but not Vav2 or Vav3. Although all three Vav isoforms existed in Jurkat cells, Rac2 was distinguishably activated by Vav1 and that led to enhanced Bcl-2 expression and cell survival. Akt was modulated downstream of Vav1-Rac2, and the activation of Akt was indispensable in the enhanced transcription of Bcl-2. Intriguingly, neither Vav2 nor Vav3 was able to activate Rac2-Akt pathway as determined by gene silencing approach. Our data illustrated a unique role of Vav1 in T leukemia survival by selectively triggering Rac2-Akt axis and elevating the expression of anti-apoptotic Bcl-2.
authors.affiliation: Key Laboratory of Microbial Functional Genomics of Ministry of Education, College of Life Sciences, Nankai University, 94 Weijin Road, Tianjin 300071, PR China.
authors.forename: Ya-Juan
authors.initials: YJ
authors.lastname: Wan
authors.affiliation: Key Laboratory of Microbial Functional Genomics of Ministry of Education, College of Life Sciences, Nankai University, 94 Weijin Road, Tianjin 300071, PR China.
authors.forename: Yin
authors.initials: Y
authors.lastname: Yang
authors.affiliation: Key Laboratory of Microbial Functional Genomics of Ministry of Education, College of Life Sciences, Nankai University, 94 Weijin Road, Tianjin 300071, PR China.
authors.forename: Qian-Li
authors.initials: QL
authors.lastname: Leng
authors.affiliation: State Key Laboratory of Medicinal Chemical Biology, College of Life Sciences, Nankai University, 94 Weijin Road, Tianjin 300071, PR China.
authors.forename: Bei
authors.initials: B
authors.lastname: Lan
authors.affiliation: Key Laboratory of Microbial Functional Genomics of Ministry of Education, College of Life Sciences, Nankai University, 94 Weijin Road, Tianjin 300071, PR China.
authors.forename: Hui-Yan
authors.initials: HY
authors.lastname: Jia
authors.affiliation: Key Laboratory of Microbial Functional Genomics of Ministry of Education, College of Life Sciences, Nankai University, 94 Weijin Road, Tianjin 300071, PR China.
authors.forename: Yao-Hui
authors.initials: YH
authors.lastname: Liu
authors.affiliation: State Key Laboratory of Medicinal Chemical Biology, College of Life Sciences, Nankai University, 94 Weijin Road, Tianjin 300071, PR China.
authors.forename: Cui-Zhu
authors.initials: CZ
authors.lastname: Zhang
authors.affiliation: Key Laboratory of Microbial Functional Genomics of Ministry of Education, College of Life Sciences, Nankai University, 94 Weijin Road, Tianjin 300071, PR China; State Key Laboratory of Medicinal Chemical Biology, College of Life Sciences, Nankai University, 94 Weijin Road, Tianjin 300071, PR China. Electronic address: caoyj@nankai.edu.cn.
authors.forename: Youjia
authors.initials: Y
authors.lastname: Cao
mesh_terms: D017209:Apoptosis; D057809:HEK293 Cells; D006801:Humans; D019169:Jurkat Cells; D007938:Leukemia / Q000378:metabolism / Q000473:pathology; D011401:Promoter Regions, Genetic; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism*; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000235:genetics / Q000378:metabolism*; D051567:Proto-Oncogene Proteins c-vav / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D034622:RNA Interference; D034741:RNA, Small Interfering / Q000378:metabolism; D020744:rac GTP-Binding Proteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D000097766:RAC2 GTP-Binding Protein
chemical_list: D051057:Proto-Oncogene Proteins c-akt; D019253:Proto-Oncogene Proteins c-bcl-2; D051567:Proto-Oncogene Proteins c-vav; D034741:RNA, Small Interfering; D020744:rac GTP-Binding Proteins; D000097766:RAC2 GTP-Binding Protein; C496618:VAV1 protein, human; C093651:VAV2 protein, human; C496621:VAV3 protein, human
keywords: Akt; Apoptosis; Bcl-2; Rac2; T leukemia cells; Vav1