ゲルミナルセンターのGα13経由のシグナリングの喪失 B細胞由来リンパ腫
Jagan R Muppidi1, Roland Schmitz2, Jesse A Green3
11] Department of Microbiology and Immunology, University of California, San Francisco, California, 94143, USA [2] Department of Medicine, University of California, San Francisco, California 94143, USA [3] Howard Hughes Medical Institute, University of California, San Francisco, California 94143, USA.
Nature
|October 3, 2014
まとめ
スフィンゴシン-1-リン酸受容体-2 (S1PR2) の変異は,生殖中心のB細胞リンパ腫でその機能を破壊する. Gα13経路は通常,成長を抑制し,拡散を防ぐが,これらのリンパ腫では頻繁に破壊される.
科学分野:
- 免疫学 免疫学とは
- 分子生物学は分子生物学である.
- 腫瘍学 腫瘍学
背景:
- ゲルミナルセンターB細胞のような拡散型大B細胞リンパ腫 (GCB-DLBCL) は,信号伝達経路と拡散因子をよく理解していない一般的な癌です.
- スフィンゴシン-1-リン酸受容体-2 (S1PR2) は,通常,生殖中心のB細胞の成長と閉じ込めを調節する.
研究 の 目的:
- GCB-DLBCLの病原性におけるS1PR2とGα13の役割を調査する.
- リンパ腫の拡散に寄与するGCB-DLBCLで破壊されたシグナル伝達経路を特定する.
主な方法:
- マウスモデルとヒトGCB-DLBCL細胞系を用いたin vitroおよびin vivoアッセイ.
- 遺伝子変異を特定するためのディープシーケンシング.
- Gα13欠乏細胞とS1PR2欠乏細胞とマウスの分析.
主要な成果:
- GCB-DLBCLに関連したS1PR2変異は,そのAktおよび移住抑制機能を損なう.
- B細胞のGα13欠乏はリンパ腫の発生とリンパと血液への拡散につながる.
- Gα13エフェクターARHGEF1の変異はまた,GCB-DLBCLの拡散を促進する.
- 孤児受容体P2RY8は,B細胞の成長と閉じ込めのGα13依存の調節体として特定されました.
結論:
- Gα13に依存する経路は,生殖中心のB細胞の成長を抑制し,拡散を防止する二重の役割を果たします.
- この経路は,GCB-DLBCLとバーキットリンパ腫では頻繁に障害され,疾患の進行に寄与します.
関連する概念動画
01:31The Intrinsic Apoptotic Pathway
9.0K
Internal cellular stress, such as cellular injury or hypoxia, triggers intrinsic apoptosis. The B-cell lymphoma 2 (Bcl-2) family of proteins are the primary regulators of the intrinsic apoptotic pathway. For example, during DNA damage, checkpoint proteins, such as Ataxia Telangiectasia Mutated (ATM protein) and Checkpoints Factor-2 (Chk2) proteins, are activated. These proteins phosphorylate p53 which further activates pro-apoptotic proteins, such as Bax, Bak, PUMA, and Noxa, and inhibits...
9.0K
01:17Intracellular Signaling Affects Focal Adhesions
3.8K
Integrins act both as extracellular input receivers and as intracellular processing activators. As their name suggests, integrins are entirely integrated into the membrane structure. Their hydrophobic membrane-spanning regions interact with the phospholipid bilayer's hydrophobic region. These membrane receptors provide extracellular attachment sites for effectors like hormones and growth factors. They activate intracellular response cascades when their effectors are bound and active.
Some...
Some...
3.8K
01:12Loss of Tumor Suppressor Gene Functions
6.2K
Tumor suppressor genes are normal genes that can slow down cell division, repair DNA mistakes, or program the cells for apoptosis in case of irreparable damage. Hence, they play an essential role in preventing the proliferation of damaged cells.
When the tumor suppressor genes develop mutations or are lost, cells start growing out of control, leading to cancer. However, a single functional copy of the tumor suppressor gene is enough for the cells to maintain their normal functions and cell...
When the tumor suppressor genes develop mutations or are lost, cells start growing out of control, leading to cancer. However, a single functional copy of the tumor suppressor gene is enough for the cells to maintain their normal functions and cell...
6.2K
01:19Interactions Between Signaling Pathways
7.7K
Signaling cascades usually lack linearity. Multiple pathways interact and regulate one another, allowing cells to integrate and respond to diverse environmental stimuli.
Convergence and divergence, and cross-talk between signaling pathways
Two distinct signaling pathways can converge on a single functional unit, which may either be a single protein or a complex of proteins. The response is either functionally distinct or synergistic between the two pathways but different from the response...
Convergence and divergence, and cross-talk between signaling pathways
Two distinct signaling pathways can converge on a single functional unit, which may either be a single protein or a complex of proteins. The response is either functionally distinct or synergistic between the two pathways but different from the response...
7.7K
03:14Notch Signaling Pathway
6.8K
The Notch signaling pathway is a major intracellular signaling pathway that is highly conserved over a broad spectrum of metazoan species. It stands unique from other intracellular signaling mechanisms in animals because notch protein itself acts as the receptor as well as the primary signaling molecule.
The Notch gene came into the limelight in 1914 after the discovery that its mutation in Drosophila melanogaster leads to a serrated (or "notched") wing margin phenotype. It was not...
The Notch gene came into the limelight in 1914 after the discovery that its mutation in Drosophila melanogaster leads to a serrated (or "notched") wing margin phenotype. It was not...
6.8K
01:15Receptor Downregulation in MVBs
2.9K
Multivesicular bodies (MVBs) are mature endosomes that sort ubiquitinated proteins and then fuse with lysosomes to degrade the sorted proteins. Epidermal growth factor (EGF) and its receptor (EGFR) form a complex that can be internalized through endocytosis, sorted into an MVB, and later degraded.
The EGFR can initiate signaling pathways that lead to cell proliferation, migration, and differentiation. Overexpression of EGFR stimulates cells to proliferate. Excessive EGFR...
The EGFR can initiate signaling pathways that lead to cell proliferation, migration, and differentiation. Overexpression of EGFR stimulates cells to proliferate. Excessive EGFR...
2.9K