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由短肽序列中的活性位點定義的胸腺素β4的生物活性

已更新:6月 2


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引用 | The FASB Jurnal報導


Biological activities of thymosin beta4 defined by active sites in short peptide sequences

Abstract 胸腺素 beta(4) 是一種普遍存在的小蛋白,含有 43 個氨基酸,通過其肌動蛋白結合域和對細胞的多種生物學影響具有結構/功能活性。由於它是真核細胞中主要的肌動蛋白螯合分子,並且基本上存在於所有細胞和體液中,因此胸腺素 β(4) 具有在組織發育、維持、修復和病理學中發揮重要作用的潛力。已經確定了幾個具有獨特功能的活性位點,包括含有 4 個氨基酸的氨基末端位點 (Ac-SDKP),通常可以阻止炎症並減少纖維化。氨基末端的另一個活性位點包含 15 個氨基酸,包括 Ac-SDKP,可促進細胞存活並阻止細胞凋亡,而包含 LKKTETQ、中央肌動蛋白結合域 (aa 17-23) 和 1 個額外氨基酸 (Q ), 促進血管生成、傷口癒合和細胞遷移。已經確定了幾種其他生物活性但尚未定位於該分子中,包括其抗菌活性、各種基因的誘導(包括層粘連蛋白 5、MMP、TGF β、zyxin、末端脫氧核苷酸轉移酶和血管生成相關蛋白),以及激活 ILK/PINCH/Akt 和其他在細胞凋亡和炎症通路中重要的信號分子的能力。本綜述詳細介紹了這些重要的生理和病理活性位點及其潛在的治療用途。zyxin、末端脫氧核苷酸轉移酶和血管生成相關蛋白),以及激活 ILK/PINCH/Akt 和其他在細胞凋亡和炎症通路中重要的信號分子的能力。本綜述詳細介紹了這些重要的生理和病理活性位點及其潛在的治療用途。zyxin、末端脫氧核苷酸轉移酶和血管生成相關蛋白),以及激活 ILK/PINCH/Akt 和其他在細胞凋亡和炎症通路中重要的信號分子的能力。本綜述詳細介紹了這些重要的生理和病理活性位點及其潛在的治療用途。 Thymosin beta(4), a small ubiquitous protein containing 43 aa, has structure/function activity via its actin-binding domain and numerous biological affects on cells. Since it is the major actin-sequestering molecule in eukaryotic cells and is found essentially in all cells and body fluids, thymosin beta(4) has the potential for significant roles in tissue development, maintenance, repair, and pathology. Several active sites with unique functions have been identified, including the amino-terminal site containing 4 aa (Ac-SDKP) that generally blocks inflammation and reduces fibrosis. Another active site at the amino terminus contains 15 aa, including Ac-SDKP, and promotes cell survival and blocks apoptosis, while a short sequence containing LKKTETQ, the central actin-binding domain (aa 17-23) plus 1 additional amino acid (Q), promotes angiogenesis, wound healing, and cell migration. Several additional biological activities have been identified but not yet localized in the molecule, including its antimicrobial activity, the induction of various genes (including laminin-5, MMPs, TGF beta, zyxin, terminal deoxynucleotidyl transferase, and angiogenesis-related proteins), and the ability to activate ILK/PINCH/Akt, and other signaling molecules important in both apoptosis and inflammatory pathways. This review details these important physiologically and pathologically active sites and their potential therapeutic uses.


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