Cell Signalling | 细胞信号传导

📚 Cell Signalling | 细胞信号传导

In multicellular organisms, individual cells must communicate with one another to coordinate metabolism, growth, differentiation and responses to the environment. Cell signalling is the molecular dialogue by which a chemical messenger or physical stimulus causes a target cell to change its behaviour. Errors in this communication network can lead to diseases such as diabetes and cancer.

在多细胞生物中，单个细胞必须相互通讯，以协调代谢、生长、分化和对环境作出反应。细胞信号传导是细胞通过化学信使或物理刺激使靶细胞改变行为的分子对话。通讯网络出错可能导致糖尿病和癌症等疾病。

1. The Need for Cell Signalling | 细胞信号传导的必要性

A cell cannot survive in isolation; it must detect nutrients, hormones, growth factors and danger signals. Signalling allows tissues to respond as a coordinated whole, for example when pancreatic beta cells release insulin to lower blood glucose after a meal. It also underlies development, immune defence and homeostasis.

细胞无法孤立生存；它必须检测营养物质、激素、生长因子和危险信号。信号传导使组织作为一个协调整体作出反应，例如进餐后胰岛β细胞释放胰岛素来降低血糖。它也是发育、免疫防御和稳态的基础。

Without signalling, cells would grow, divide and die in an unregulated manner. Signalling networks control cell number, cell position and cell function, and their breakdown is a central feature of many disorders.

没有信号传导，细胞就会以不受调控的方式生长、分裂和死亡。信号网络控制细胞数量、位置和功能，其崩溃是许多疾病的核心特征。

2. Forms of Cell Signalling | 细胞信号传导的形式

Signalling may be endocrine, paracrine, autocrine or synaptic. Endocrine signalling uses hormones transported in blood to distant targets; paracrine signalling acts on neighbouring cells; autocrine signalling acts on the same cell or identical nearby cells; synaptic signalling is a specialised rapid form in which neurotransmitters cross a synapse.

信号传导可以是内分泌、旁分泌、自分泌或突触。内分泌信号利用激素经血液运输到远处靶细胞；旁分泌作用于邻近细胞；自分泌作用于自身或同类附近细胞；突触信号是一种专门的快速形式，神经递质跨突触传递。

Hydrophobic messengers can enter cells, while most hydrophilic messengers cannot cross the plasma membrane and therefore rely on membrane receptors. This distinction explains why steroid hormones and gases such as nitric oxide have different receptor locations from peptide hormones.

疏水性信使可以进入细胞，而大多数亲水性信使不能穿过质膜，因此依赖膜受体。这一区别解释了为什么类固醇激素和一氧化氮等气体的受体位置与肽类激素不同。

3. Ligands and Receptors | 配体与受体

A ligand is any molecule that binds specifically to a receptor protein. Binding is reversible and changes the shape of the receptor; this conformational change is the first step in converting an extracellular signal into an intracellular response. Receptors show high specificity and saturation, similar to enzymes.

配体是任何能特异性结合受体蛋白的分子。结合是可逆的，并改变受体的形状；这种构象变化是将细胞外信号转化为细胞内反应的第一步。受体具有高度特异性和饱和性，与酶类似。

Agonists mimic natural ligands and activate receptors, whereas antagonists bind without activating them and block signalling. Many medicines act as antagonists, for example beta-blockers block adrenaline receptors on heart muscle.

激动剂模拟天然配体并激活受体，而拮抗剂结合但不激活，从而阻断信号传导。许多药物作为拮抗剂起作用，例如β受体阻滞剂阻断心肌上的肾上腺素受体。

4. Intracellular Receptors: Steroid Hormones | 细胞内受体：类固醇激素

Lipid-soluble ligands such as steroid hormones, thyroid hormones and nitric oxide pass through the plasma membrane. Testosterone and oestradiol bind to intracellular receptors in the cytoplasm; the hormone-receptor complex moves into the nucleus and acts as a transcription factor, switching specific genes on.

脂溶性配体如类固醇激素、甲状腺激素和一氧化氮可以穿过质膜。睾酮和雌二醇与细胞质中的细胞内受体结合；激素-受体复合物进入细胞核，作为转录因子开启特定基因。

Because gene transcription and protein synthesis take time, intracellular receptor responses are relatively slow but long-lasting. This explains why steroid hormones control long-term processes such as puberty and development rather than rapid reflexes.

由于基因转录和蛋白质合成需要时间，细胞内受体的反应相对较慢但持久。这解释了为什么类固醇激素控制青春期和发育等长期过程，而不是快速反射。

5. Cell-Surface Receptors and Transduction | 细胞表面受体与信号转导

Hydrophilic ligands, including peptide hormones and neurotransmitters, bind to cell-surface receptors. The receptor spans the plasma membrane; ligand binding on the outside triggers a change on the cytoplasmic side. This activates a signal transduction cascade, often by generating second messengers or activating protein kinases.

亲水性配体，包括肽类激素和神经递质，与细胞表面受体结合。受体跨过质膜；外侧配体结合引发胞质侧变化。这激活信号转导级联，通常通过产生第二信使或激活蛋白激酶。

Signal transduction amplifies the message: one receptor-ligand complex can activate many enzymes, and each enzyme can generate many product molecules. The result is a large cellular response from very few ligand molecules.

信号转导具有放大作用：一个受体-配体复合物可以激活许多酶，每个酶又生成大量产物分子。因此极少配体分子就能引起很大的细胞反应。

6. G Protein-Coupled Receptors | G蛋白偶联受体

G protein-coupled receptors (GPCRs) are a large family with seven transmembrane α-helices. When a ligand binds, the receptor activates a G protein by causing it to exchange GDP for GTP. The activated G protein then stimulates an effector enzyme such as adenylyl cyclase.

G蛋白偶联受体是一个具有七个跨膜α螺旋的大蛋白家族。当配体结合时，受体使G蛋白将GDP交换为GTP，从而激活G蛋白。活化的G蛋白随后刺激效应酶，如腺苷酸环化酶。

GPCR systems mediate many physiological responses. Examples include adrenaline acting through β-adrenergic receptors, glucagon in liver cells and light detection by rhodopsin in rod cells.

GPCR系统介导许多生理反应。例如肾上腺素通过β-肾上腺素受体起作用、肝细胞中的胰高血糖素，以及视杆细胞中视紫红质对光的检测。

7. cAMP as a Second Messenger | 作为第二信使的cAMP

Adenylyl cyclase converts ATP into cyclic AMP; the reaction removes pyrophosphate. cAMP is a second messenger because it relays the extracellular signal to intracellular targets. It activates protein kinase A (PKA), which phosphorylates specific serine or threonine residues on target proteins.

腺苷酸环化酶将ATP转化为环磷酸腺苷；该反应去除焦磷酸。cAMP是第二信使，因为它将细胞外信号传递给细胞内靶点。它激活蛋白激酶A（PKA），PKA磷酸化靶蛋白上特定的丝氨酸或苏氨酸残基。

ATP → cAMP + PPᵢ

Phosphorylation changes enzyme activity, membrane permeability or transcription factor activity. For example, in liver cells cAMP-dependent phosphorylation activates enzymes that break down glycogen, releasing glucose during the fight-or-flight response.

磷酸化改变酶活性、膜通透性或转录因子活性。例如在肝细胞中，cAMP依赖性磷酸化激活分解糖原的酶，在战斗或逃跑反应中释放葡萄糖。

The signal is switched off when phosphodiesterase hydrolyses cAMP to AMP and protein phosphatases remove phosphate groups. This rapid termination allows cells to respond again to new signals.

当磷酸二酯酶将cAMP水解为AMP、蛋白磷酸酶去除磷酸基团时，信号被关闭。这种快速终止使细胞能够再次对新信号作出反应。

8. Calcium Ions as Second Messengers | 作为第二信使的钙离子

Calcium ions are kept at very low concentration in the cytosol, about 100 nmol dm⁻³, by Ca²⁺-ATPases and Na⁺-Ca²⁺ exchangers. Many signalling pathways open calcium channels in the endoplasmic reticulum or plasma membrane, producing a rapid rise in cytosolic Ca²⁺.

细胞质中钙离子浓度保持很低，约为100 nmol dm⁻³，依靠Ca²⁺-ATP酶和Na⁺-Ca²⁺交换体维持。许多信号通路打开内质网或质膜上的钙通道，使胞质Ca²⁺快速升高。

Calcium binds to the protein calmodulin, inducing a shape change. The Ca²⁺-calmodulin complex activates protein kinases and other enzymes, leading to responses such as smooth muscle contraction, neurotransmitter release and egg fertilisation.

钙与钙调蛋白结合，引起形状改变。Ca²⁺-钙调蛋白复合物激活蛋白激酶和其他酶，引起平滑肌收缩、神经递质释放和卵细胞受精等反应。

9. Receptor Tyrosine Kinases | 受体酪氨酸激酶

Receptor tyrosine kinases (RTKs) have an extracellular ligand-binding domain and an intracellular tyrosine kinase domain. Growth factors such as epidermal growth factor bind and cause two receptor molecules to dimerise. Each receptor phosphorylates tyrosine residues on its partner; this is autophosphorylation.

受体酪氨酸激酶有一个胞外配体结合域和一个胞内酪氨酸激酶域。表皮生长因子等生长因子结合后使两个受体分子二聚化。每个受体磷酸化对方受体上的酪氨酸残基，即自磷酸化。

Phosphorylated tyrosine residues serve as docking sites for relay proteins such as Ras. The Ras-MAP kinase cascade carries the signal to the nucleus and promotes cell division. Overactive RTK pathways are common in cancer cells.

磷酸化酪氨酸残基作为Ras等接力蛋白的停靠位点。Ras-MAP激酶级联将信号传递到细胞核，促进细胞分裂。受体酪氨酸激酶通路过度活跃常见于癌细胞。

10. Cellular Responses and Gene Expression | 细胞应答与基因表达

The final outcome of a signalling pathway may be metabolic, electrical or transcriptional. Some responses occur within seconds, such as adrenaline increasing heart rate; others take hours, such as steroid hormones altering gene expression.

信号通路的最终结果可能是代谢、电学或转录方面的变化。有些反应在几秒内发生，如肾上腺素加快心率；另一些需要数小时，如类固醇激素改变基因表达。

Signal specificity depends on the receptor and the intracellular proteins present in a given cell. The same ligand can produce different responses: acetylcholine slows the heart but contracts skeletal muscle and stimulates secretion in salivary glands.

信号特异性取决于特定细胞中的受体和胞内蛋白质。同一配体可以产生不同反应：乙酰胆碱使心跳减慢，但使骨骼肌收缩，并刺激唾液腺分泌。

11. Apoptosis: Regulated Cell Death | 细胞凋亡：受调控的细胞死亡

Apoptosis is programmed cell death that removes damaged, infected or surplus cells without triggering inflammation. The cell shrinks, its chromatin condenses, the membrane blebs, and the cell breaks into small apoptotic bodies that are engulfed by phagocytes.

细胞凋亡是一种程序性细胞死亡，可在不引发炎症的情况下清除受损、感染或多余的细胞。细胞皱缩、染色质凝集、膜出泡，细胞分裂成小凋亡体，被吞噬细胞吞噬。

Apoptosis is controlled by internal and external signals. Internal signals include DNA damage detected by p53; external signals include death ligands binding to death receptors. These activate caspase enzymes, which cleave key proteins and activate DNases that fragment DNA.

细胞凋亡受内部和外部信号控制。内部信号包括p53检测到DNA损伤；外部信号包括死亡配体与死亡受体结合。这些信号激活半胱天冬酶，切割关键蛋白，并激活使DNA片段化的DNA酶。

The balance between pro-apoptotic and anti-apoptotic proteins such as Bax and Bcl-2 determines whether a cell survives. This is important during development, for example in removing webbing between fingers, and in preventing tumour formation.

促凋亡蛋白和抗凋亡蛋白（如Bax和Bcl-2）之间的平衡决定细胞是否存活。这在发育过程中很重要，例如去除手指间的蹼，也在预防肿瘤形成中发挥作用。

12. Signalling Errors and Cancer | 信号错误与癌症

Cancer often results from mutations that make signalling pathways permanently active. For example, mutant Ras proteins may remain bound to GTP and continuously stimulate cell division. Overexpression of growth factor receptors can also make cells hypersensitive to growth signals.

癌症常由信号通路永久激活的突变引起。例如，突变Ras蛋白可能一直与GTP结合，持续刺激细胞分裂。生长因子受体过表达也会使细胞对生长信号过度敏感。

Many targeted cancer therapies block overactive signalling molecules. Imatinib inhibits a mutant tyrosine kinase in chronic myeloid leukaemia; trastuzumab blocks

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Cell Signalling | 细胞信号传导