细胞生物学_cell signaling
单词
Extracellular 细胞外的
Signal Molecules 信号分子
Intracellular 细胞内的
Second Messengers 第二信使
Enzymatic Cascades 酶级联反应
Endocrine Signaling 内分泌信号
Hormone 激素
Paracrine Signaling 旁分泌信号
Growth Factor 生长因子
Autocrine Signaling 自分泌信号
Synaptic Signaling 突触信号
Neurotransmitter 神经递质
Contact-dependent Signaling 接触依赖性信号
Nuclear Receptor Superfamily 核受体超家族
Hydrophobic Signal Molecules 疏水性信号分子
Ion-Channel-Coupled Receptors 离子通道偶联受体
G-Protein-Coupled Receptors G蛋白偶联受体
Enzyme-Coupled Receptors 酶偶联受体
Cytosol 细胞质
Lipid-Soluble 脂溶性
Molecular Switch 分子开关
Kinase Cascades 激酶级联反应
GTP-Binding Protein GTP结合蛋白
Desensitization 脱敏
Receptor Sequestration 受体隔离
Receptor Down-Regulation 受体下调
Receptor Inactivation 受体失活
Enzyme-Coupled Receptors 酶联受体
Receptor Tyrosine Kinase 受体酪氨酸激酶
Dimerize 二聚
Phosphorylating 磷酸化
Raf(MAPKKK) 丝裂原活化蛋白激酶激酶激酶
MEK(MAPKK) 丝裂原活化蛋白激酶激酶
ERK(MAPK) 丝裂原活化蛋白激酶
Transcription Regulatory Protein 转录调控蛋白
PI3K 磷脂酰肌醇3激酶
PI(3,4,5)P3 磷脂酰肌醇3,4,5-三磷酸
PDK1 磷脂依赖性激酶1
AKT 蛋白激酶B
Tyrosine-Kinase-Associated Receptors 酪氨酸激酶相关受体
Cytokine Receptors 细胞因子受体
Janus Kinases (JAKs) Janus激酶(JAKs)
Signal Transducer and Activator of Transcription 信号转导子和转录激活子
Receptor Serine/Threonine Kinases 受体丝氨酸/苏氨酸激酶
TGFβ 转化生长因子β
principle of signaling
一些句子
Each Cell Is Programmed to Respond to Specific Combinations of Extracellular Signals.
Extracellular Signal Molecules Bind to Specific Receptors.
A signal molecule often has different effects on different types of target cells.
Cell-Surface Receptors Relay Signals Via Intracellular Signaling Molecules.
Second Messengers and Enzymatic Cascades Amplify Signals.
The Speed of a Response Depends on the Turnover of Signaling Molecules.
Cells Can Adjust Their Sensitivity to a Signal.
Extracellular Signals Can Act Over Short or Long Distances
1. Signaling dependent on secreted signal molecules
1.endocrine signaling 内分泌
信号分子 hormone 激素
2.paracrine signaling 旁分泌
信号分子 growth factor 生长因子
3.autocrine signaling 自分泌
eg.癌细胞
4.synaptic signaling 突触信号
信号分子 neurotransmitter 神经递质
2.Contact-dependent signaling
receptors
intracellular receptors
Intracellular receptors belong to nuclear receptor superfamily核受体超家族.
The receptor ligand complex acts as a transcription factor in the nucleus.
hydrophobic signal molecules信号分子疏水
调控转录
cell-surface receptors
1.ion-channel-coupled receptors
2.G-protein-coupled receptors
G-protein代表trimeric GPT-binding protein
3.enzyme-coupled receptors
function as enzymes or associate directly with enzymes that they activate
cell surface receptor通过细胞内信号分子转导信号
second messengers 第二信使
受体激活后产生大量小分子信号散布到细胞的各个部分
water soluble水溶性,在cytosl细胞质中扩散
eg.cAMP,Ca2+
Lipid-soluble脂溶性,在cell membrane细胞膜中扩散
eg.DAG
molecular switch 分子开关
分子开关本身是一个激酶,可以结合pi或GTP从而活化,进而催化下一个分子开关的活化
产生kinase cascades 激酶级联反应
1.activated by pi
2.GTP-binding protein
signaling through G-protein-coupled receptors
总览
GPCRs
G-protein-coupled receptors
最大的细胞表面受体家族
GPCR都通过Trimeric G 蛋白转导信号
GPCRs 结构
single polypeptide chain 单个多肽链
the chain threads back and forth across the lipid bilayer 7 times 这个链穿过脂质双分子层7次
form a cylindrical structure 圆柱形
a deep ligand-biding site at center
Trimeric G protein
结构
有三个亚基
α亚基是GTPase,被GTP调控的分子开关
机理
Activation of a G protein by an activated GPCR
路径
1.GPCRs → G protein → ac → cAMP → PKA → target protein
可以induce rapid response
eg.肾上腺素加速糖原分解
也可以induce slow response
eg.PKA从核孔进入激活指导转录的蛋白
2.GPCRs → G proteins → PLC → DAG&IP3 →
Ca2+可以激活calmodulin钙调蛋白,钙调蛋白可以bind to 并激活其他蛋白
PKC可以激活基因转录
3.GPCRs → G protein → ion channels
GPCRs Desensitization脱敏
The desensitization of the GPCRs depends on their phosphorylation by PKA, PKC, or a member of the family of GPCR kinases (GRKs)
1.receptor sequestration
受体隔离，被收到细胞里
2.receptor down-regulation
受体下调，被溶酶体吃掉
3.receptor inactivation
受体脱敏，构象变化
signaling through enzyme-couplued receptors
通常酶联受体只有一部分穿过膜
RTKs
receptor tyrosine kinase 受体酪氨酸激酶
激活
signal protein会导致两个RTKs dimerize二聚
然后phosphorylating 自己的络氨酸残基
或者并不通过磷酸化activate而是通过conformational changes 构象变化
激活后
Phosphorylated tyrosines on RTKs serve as docking sites for intracellular
signaling proteins
磷酸化的络氨酸作为信号蛋白的停靠位点
磷酸化的络氨酸可以结合有SH2 domain / PTB domain的信号蛋白
路径
1.RTKs → Ras → Raf(MAPKKK) → MEK(MAPKK) → ERK(MAPK) → nucleus → transcription regulatory protein
RTKs可以激活Ras
MAP 是 mitogen-activated protein
中间的一整坨叫 MAP kinase module
这一坨东西有scaffold protein支架蛋白固定防止cross-talk干扰
2.RTKs → PI3K → PI(3,4,5)P3 → PDK1 → AKT → target protein
这条通路刺激动物细胞生存并长大
tyrosine-kinase-associated receptors
连着络氨酸激酶的一种受体
这种receptor与细胞质内的络氨酸激酶associate
本身并不能催化络氨酸
期中最大的一类是cytokine receptors
cytokine receptors 细胞因子受体
activate JAK-STAT signaling pathway
These receptors are stably associated with cytoplasmic tyrosine kinases called
Janus kinases (JAKs)
JAKs phosphorylate and activate transcription regulators called STATs (signal transducer信号转到子 and activator of transcription转录激活因子)
receptor serine/threonine kinases
主要介导TGFβ的信号
alternative signaling routes in gene regulation
还好几页ppt,不想写了,估计不考
总结
