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TAM 激酶作为细胞死亡的调节因子。

TAM kinases as regulators of cell death.

机构信息

Department of Leukemia, The University of Texas MD Anderson Cancer Center, Houston, TX, United States of America.

Department of Leukemia, The University of Texas MD Anderson Cancer Center, Houston, TX, United States of America; Section of Molecular Hematology and Therapy, The University of Texas MD Anderson Cancer Center, Houston, TX, United States of America.

出版信息

Biochim Biophys Acta Mol Cell Res. 2021 May;1868(6):118992. doi: 10.1016/j.bbamcr.2021.118992. Epub 2021 Feb 27.

Abstract

Receptor Tyrosine Kinases are critical regulators of signal transduction that support cell survival, proliferation, and differentiation. Dysregulation of normal Receptor Tyrosine Kinase function by mutation or other activity-altering event can be oncogenic or can impact the transformed malignant cell so it becomes particularly resistant to stress challenge, have increased proliferation, become evasive to immune surveillance, and may be more prone to metastasis of the tumor to other organ sites. The TAM family of Receptor Tyrosine Kinases (TYRO3, AXL, MERTK) is emerging as important components of malignant cell survival in many cancers. The TAM kinases are important regulators of cellular homeostasis and proper cell differentiation in normal cells as receptors for their ligands GAS6 and Protein S. They also are critical to immune and inflammatory processes. In malignant cells, the TAM kinases can act as ligand independent co-receptors to mutant Receptor Tyrosine Kinases and in some cases (e.g. FLT3-ITD mutant) are required for their function. They also have a role in immune checkpoint surveillance. At the time of this review, the Covid-19 pandemic poses a global threat to world health. TAM kinases play an important role in host response to many viruses and it is suggested the TAM kinases may be important in aspects of Covid-19 biology. This review will cover the TAM kinases and their role in these processes.

摘要

受体酪氨酸激酶是信号转导的关键调节因子,支持细胞的存活、增殖和分化。正常受体酪氨酸激酶功能的失调,如突变或其他改变活性的事件,可能致癌,或影响转化的恶性细胞,使其特别耐受应激挑战,增殖增加,逃避免疫监视,并可能更容易发生肿瘤向其他器官部位的转移。受体酪氨酸激酶(TYRO3、AXL、MERTK)的 TAM 家族作为许多癌症中恶性细胞存活的重要组成部分正在出现。TAM 激酶是正常细胞中细胞内稳态和适当细胞分化的重要调节剂,作为其配体 GAS6 和蛋白 S 的受体。它们对免疫和炎症过程也很关键。在恶性细胞中,TAM 激酶可以作为配体非依赖性共受体与突变的受体酪氨酸激酶结合,在某些情况下(例如 FLT3-ITD 突变),它们的功能是必需的。它们在免疫检查点监测中也有作用。在撰写本综述时,Covid-19 大流行对全球健康构成了威胁。TAM 激酶在宿主对许多病毒的反应中起着重要作用,有人认为 TAM 激酶在 Covid-19 生物学的某些方面可能很重要。这篇综述将涵盖 TAM 激酶及其在这些过程中的作用。

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