Roles ofRacregulatorsinpathogenesisofleukemia

Racregulators在白血病发病机制中的作用

• 批准号: 21591199
• 负责人: KATSUMI Akira
• 金额: $ 2.83万
• 依托单位: National Center for Geriatrics and Gerontology (2010-2011)Nagoya University (2009)
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2009
• 资助国家: 日本
• 起止时间: 2009 至 2011
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-21591199/
• 关键词: 血液内科学; 細胞接着; Rho family; 急性白血病; GAP; Rac; RhoH; GEF; Rho; 抗接着治療

Rho GTPases have been widely studied because they are critical regulators of cellularsignaling mediated by G-protein-coupled receptors, tyrosine kinase receptors and integrins. RhoH, a member of the Rho family, is specifically expressed in the hematopoietic cells, including bone marrow progenitor, differentiated myeloid andlymphoid cells. RhoH antagonizes Rac, however, the molecules that inactivate Racdownstream of RhoH have not been identified. Here we perform GTP-RhoH affinity column chromatography. Using triple quadrupole liquid chromatography tandemmass spectrometer, 83 different proteins associated with active RhoH were identified. They include Rho GTPase activating proteins(RhoGAP), serine/threonine kinases, phosphatidylinositol kinases, and others. Among them, focused on T-cell activationRhoGTPaseactivatingprotein(TAGAP), whichisspecweifically expressed inthe hematopoietic cells. TAGAP binds to RhoH through its GAP domain. Expression of both full length and GAP domain of TAGAP effectively deactivates Rac, whereas GAP domain deleted TAGAP did not. These results suggest that RhoH negatively regulates Rac through TAGAP.

Rho GTPases是G蛋白偶联受体、酪氨酸激酶受体和整合素介导的细胞信号转导的重要调节因子，因此得到了广泛的研究。RhoH是Rho家族成员之一，在造血细胞中特异性表达，包括骨髓祖细胞、分化的髓系细胞和淋巴样细胞。RhoH拮抗Rac，然而，在RhoH下游抑制Rac的分子尚未被鉴定。在这里，我们进行GTP-RhoH亲和柱层析。用三重四极杆液相色谱-质谱联用仪鉴定了83种与活性RhoH相关的蛋白质。它们包括Rho GTP酶激活蛋白（RhoGAP）、丝氨酸/苏氨酸激酶、磷脂酰肌醇激酶等。其中，T细胞活化的RhoGTPaseactivatingprotein（TAGAP）是造血细胞特异性表达的蛋白质。TAGAP通过其GAP结构域与RhoH结合。TAGAP的全长和GAP结构域的表达有效地使Rac失活，而GAP结构域缺失的TAGAP则不能。这些结果表明RhoH通过TAGAP负调控Rac。

项目成果

Mutation of ARHGAP9 in patients with coronary spastic angina

• DOI: 10.1038/jhg.2009.120
• 发表时间: 2010-01-01
• 期刊: JOURNAL OF HUMAN GENETICS
• 影响因子: 3.5
• 作者: Takefuji, Mikito;Asano, Hiroyuki;Kaibuchi, Kozo
• 通讯作者: Kaibuchi, Kozo

FLT3/ITD regulates leukaemia cell adhesion throughα4β1 integrin and Pyk2 signaling

FLT3/ITD 通过 α4β1 整合素和 Pyk2 信号传导调节白血病细胞粘附

• 发表时间: 2011
• 期刊: Eur J Haematol
• 影响因子: 3.1
• 作者: Katsumi A;Kaibuchi K
• 通讯作者: Kaibuchi K

Glanzmann thrombasthenia detected because of knee hemarthrosis : a case report

因膝关节积血而检测出血小板无力症：病例报告

• 发表时间: 2010
• 期刊: J Pediatr Orthop B
• 影响因子: 1.1
• 作者: Urakawa H;Nishida Y;Tsukushi S;Katsumi A Ishiguro N
• 通讯作者: Katsumi A Ishiguro N

TLK199～骨髄異形成症候群の治療～

TLK199 ~骨髓增生异常综合征的治疗~

• 发表时间: 2010
• 期刊: 血液フロンティア
• 作者: Suzuki K;Ono R;Ohishi K;Katayama N;Syuichi Miyawaki;勝見章
• 通讯作者: 勝見章

Definite diagnosis in Japanese patients with protein C deficiency by identification of causative PROC mutations

通过确定致病性 PROC 突变对日本蛋白 C 缺乏症患者进行明确诊断

• 发表时间: 2010
• 期刊: Int J Hematol
• 影响因子: 2.1
• 作者: Takagi A;Tanaka R;Nakashima D;Fujimori Y;Yamada T;Okumura K;Murate T;Yamada M;Horikoshi Y;Yamamoto K;Katsumi A
• 通讯作者: Katsumi A