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相关概念视频

Protein Kinases and Phosphatases02:54

Protein Kinases and Phosphatases

Proteins undergo chemical modifications that trigger changes in the charge, structure, and conformation of the proteins. Phosphorylation, acetylation, glycosylation, nitrosylation, ubiquitination, lipidation, methylation, and proteolysis are various protein modifications that regulate protein activity. Such modifications are usually enzyme-driven.
Protein kinases
Many proteins in the cell are regulated by phosphorylation, the addition of a phosphate group. A family of enzymes called kinases...
Receptor Downregulation in MVBs01:15

Receptor Downregulation in MVBs

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 activation may...
Amplifying Signals via Enzymatic Cascade01:22

Amplifying Signals via Enzymatic Cascade

When a ligand binds to a cell-surface receptor, the receptor's intracellular domain changes shape, which may either activate its enzyme function or allow its binding to other molecules. The initial signal is amplified by most signal transduction pathways. This means that a single ligand molecule can activate multiple molecules of a downstream target. Proteins that relay a signal are most commonly phosphorylated at one or more sites, activating or inactivating the protein. Kinases catalyze the...
Receptor Tyrosine Kinases01:26

Receptor Tyrosine Kinases

Receptor tyrosine kinases or RTKs are membrane-bound receptors that phosphorylate specific tyrosine on protein substrates. RTKs regulate cellular growth, differentiation, survival, and migration. They contain an extracellular ligand binding domain, a transmembrane domain, and a cytosolic tail with intrinsic kinase activity. Several extracellular signaling molecules activate RTKs in one or more ways and relay the signal downstream. Ligands such as platelet-derived growth factor (PDGF) or...
MAPK Signaling Cascades01:07

MAPK Signaling Cascades

Mitogen-activated protein kinase, or MAPK pathway, activates three sequential kinases to regulate cellular responses such as proliferation, differentiation, survival, and apoptosis. The canonical MAPK pathway starts with a mitogen or growth factor binding to an RTK. The activated RTKs stimulate Ras, which recruits Raf or MAP3 Kinase (MAPKKK), the first kinase of the MAPK signaling cascade. Raf further phosphorylates and activates MEK or MAP2 Kinases (MAPKK), which in turn phosphorylates MAP...
The JAK-STAT Signaling Pathway01:20

The JAK-STAT Signaling Pathway

Several cytokine receptors have tightly bound Janus kinase or JAK proteins attached at their cytosolic tail. Small signaling molecules such as cytokines, growth hormones, or prolactins bind to the cytokine receptors and initiate their dimerization. The dimerization brings the cytosolic JAKs together that trans-phosphorylate and activates each other. The activated JAKs now phosphorylate cytosolic tails of the cytokine receptors, which serve as binding sites for adaptor proteins such as  SH2...

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相关实验视频

Updated: Jul 7, 2026

Characterize Disease-related Mutants of RAF Family Kinases by Using a Set of Practical and Feasible Methods
07:49

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通过氨酸酸化来缓解原瘤基因Vav的Dbl同质域的自身抑制的结构基础.

B Aghazadeh1, W E Lowry, X Y Huang

  • 1Cellular Biochemistry and Biophysics Program, Memorial Sloan-Kettering Cancer Center, New York, New York 10021, USA.

Cell
|September 28, 2000
PubMed
概括

对mVav1蛋白的铁酸化.

科学领域:

  • 分子生物学分子生物学
  • 细胞信号传递 细胞信号传递
  • 生物化学 生物化学

背景情况:

  • 罗族GTPases调节细胞形状,运动性和增殖.
  • Dbl同质 (DH) 域蛋白通过催化GDP/GTP交换激活Rho GTPases.
  • 氨酸核酸交换因子 (GEF) 活性由受体信号刺激,涉及氨酸酸化.

研究的目的:

  • 阐明mVav1自身抑制和激活的结构机制.
  • 为了研究氨酸酸化在调节mVav1 GEF活性中的作用.

主要方法:

  • 对于mVav1 DH域的结构确定,使用X射线晶体学.
  • 位点定向的突变发生改变Tyr174酸化位点.
  • 核磁共振 (NMR) 谱学用于研究形状变化.

主要成果:

  • mVav1 DH 域通过 N 终端延伸自抑制,阻断 GTPase 相互作用部位.
  • 含有Tyr174的N端的酸化或截断可以缓解自身抑制.
  • 酸化导致N端变得不结构化,并从DH域释放出来.

结论:

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  • 在Tyr174中氨酸酸化是mVav1激活的关键调节机制.
  • 自抑制性N端延伸的酸化诱导释放暴露了DH域的GTPase结合表面.
  • 这种结构机制对于细胞过程中的Vav介导信号转导至关重要.