Ras-Raf-MAPK, mTOR-PI3K-AKT信号通路详解PPT学习课件
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Effector protein– produces a mobile second messenger such as cAMP. In the case of cAMP, the effector protein is adenylate cyclase (also called adenylyl cyclase).
Ligand-Receptor binding is an reversible equilibrium process, obeying the law of mass
Receptors Properties:
• Specificity
• Saturability
• High affinity
• Reversibility
2. Ras-Raf-MAPK pathway 3. PI3K/AKT/mTOR pathway 4. Jak-STAT pathway 5. NF-kB pathway 6. Notch pathway 7. Abnormal Cell signaling and diseases
2
OVERVIEW
Distribution:
• Cell surface receptors • Intracellular receptors
8
Domains of cell surface receptors:
• The extracellular segment---binding site
• The hydrophobic membrane spanning segment--- Transmembrane （ highly conserved）
Signal Transduction Pathways & the Clinical Implications
1
CONTENT
1. Overview: Concept, components, common features of cell signal transduction pathways
Motility
Death Transformation
Cell signaling affects virtually EVERY ASPECT of cell structures and functions. 4
COMPONENTS
1. Extracellular signal molecules: Ligand/Agonist. 2. Receptor –are specific proteins, which are able to recognize and bind to corresponding ligands. Binding is specific, but not always in 1-1 fashion. 3. Transducers – carries the message from the receptor to the
Testosterone, and other lipid soluble factors, such as RA, travels through the blood and enters cells throughout the body.
In the cytoplasm, they bind and activate receptor proteins.
8. External signals induce two direct cellular responses: (1) changes the activity of pre-existed proteins (2) changes in gene expression.
12
cell membrane receptors
to a receptor protein in the cytoplasm, activating it.
3 The hormone-
receptor complex enters the nucleus and binds to specific genes.
4 The bound protein stimulates the transcription of the gene into mRNA.
1. act as cell’s ‘letter boxes’, and receive messages
2. Transmit a message into the cell, which normally leads to a specific cellular effect
3. Each cell has multiple specific receptors, making it responsive to different chemicals.
• The cytoplasmic segment---enzyme domain（ highly conserved），transferring a phosphate group from ATP to tyrosine or serine/threonine on a substrate protein.
3
Schematic view of Cell signaling
Growth factors
Signals Cytokines Extracellular matrix proteins
Cell stresses
Biochemical processes
Proliferation Differentiation
Effector protein
11
common features of cell signaling
1. Receptors could either be cell membrane or nuclear receptors. 2. a relatively small number of mechanisms have been employed. 3. conserved intracellular proteins play key roles in different signaling pathways. 4. different signaling pathways are re-used in different contexts. 5. Amplification of external signals is often necessary. 6. Convergence, divergence, and crosstalk among different signaling pathways. 7. Desensitization of receptors.
Definition
Signal transduction refers to the process that the extracellular stimuli regulate the biological functions, through membranous or intracellular receptors mediated signal cascade.
most water-soluble molecules/factors bind to cell membrane receptors and activate the signaling transduction pathway.
13
Signaling pathway via nuclear receptor
5 The mRNA is translated into a specific protein.
14
Other features: Signal Flow is not always in 1-1 fashion
Signal Receptor Transducer
Targets Response
9
Intracellular proteins
Different Kinds of intracellular proteins serve different purposes
1. Relay proteins 2. Messenger proteins 3. Adaptor proteins 4. Amplifier proteins 5. Transducer proteins 6. Bifurcation proteins 7. Integrator proteins 8. Latent gene regulatory proteins
Types of signal molecules— Lipid-soluble molecules Water-soluble molecules Gaseous molecules (NO)
Properties of signal molecules— Specificity, highly efficient, competitive Dosage-dependent, saturable Reversible, can be deactivated
5
Signal molecules
Ligand/Agonist
Proteins and peptides:
Hormones, cytokines
Bind to Amino acid derivatives: membrane Catecholamine receptors
Chemical Signal
effector. Transducers could be enzymes, adaptor, or others. Transduction is a multi-step process. 4. Effector proteins – produces a 2nd messenger such as cAMP.
These activated proteins enter the nucleus and turn on target genes .
1 The steroid
hormone testosterone passes through the plasma membrane.
2 Testosterone binds
6
1. Extracellular signal molecules: Ligand/Agonist are normally released by signal-producing cells, reach and bind to the receptor protein of target cell CONTEXT-DEPENDENT EFFECTS
Each cell is programmed to respond to a specific combinations of extracellular signal molecules, but the final read-outs are context-dependent
Fatty acid derivatives:
Prostaglandins
Extracellular molecules
Bind to
intracellular-- Steroid hormones,
receptors
Thyroxine , VD3
Physical Signal
light, wave, voice, pressure & temperature
7
2. Receptor proteins –are specific proteins, which are able to recognize and bind to corresponding ligands, and transduce signal to next signaling molecules inside of the cell.
Effector protein– produces a mobile second messenger such as cAMP. In the case of cAMP, the effector protein is adenylate cyclase (also called adenylyl cyclase).
Ligand-Receptor binding is an reversible equilibrium process, obeying the law of mass
Receptors Properties:
• Specificity
• Saturability
• High affinity
• Reversibility
2. Ras-Raf-MAPK pathway 3. PI3K/AKT/mTOR pathway 4. Jak-STAT pathway 5. NF-kB pathway 6. Notch pathway 7. Abnormal Cell signaling and diseases
2
OVERVIEW
Distribution:
• Cell surface receptors • Intracellular receptors
8
Domains of cell surface receptors:
• The extracellular segment---binding site
• The hydrophobic membrane spanning segment--- Transmembrane （ highly conserved）
Signal Transduction Pathways & the Clinical Implications
1
CONTENT
1. Overview: Concept, components, common features of cell signal transduction pathways
Motility
Death Transformation
Cell signaling affects virtually EVERY ASPECT of cell structures and functions. 4
COMPONENTS
1. Extracellular signal molecules: Ligand/Agonist. 2. Receptor –are specific proteins, which are able to recognize and bind to corresponding ligands. Binding is specific, but not always in 1-1 fashion. 3. Transducers – carries the message from the receptor to the
Testosterone, and other lipid soluble factors, such as RA, travels through the blood and enters cells throughout the body.
In the cytoplasm, they bind and activate receptor proteins.
8. External signals induce two direct cellular responses: (1) changes the activity of pre-existed proteins (2) changes in gene expression.
12
cell membrane receptors
to a receptor protein in the cytoplasm, activating it.
3 The hormone-
receptor complex enters the nucleus and binds to specific genes.
4 The bound protein stimulates the transcription of the gene into mRNA.
1. act as cell’s ‘letter boxes’, and receive messages
2. Transmit a message into the cell, which normally leads to a specific cellular effect
3. Each cell has multiple specific receptors, making it responsive to different chemicals.
• The cytoplasmic segment---enzyme domain（ highly conserved），transferring a phosphate group from ATP to tyrosine or serine/threonine on a substrate protein.
3
Schematic view of Cell signaling
Growth factors
Signals Cytokines Extracellular matrix proteins
Cell stresses
Biochemical processes
Proliferation Differentiation
Effector protein
11
common features of cell signaling
1. Receptors could either be cell membrane or nuclear receptors. 2. a relatively small number of mechanisms have been employed. 3. conserved intracellular proteins play key roles in different signaling pathways. 4. different signaling pathways are re-used in different contexts. 5. Amplification of external signals is often necessary. 6. Convergence, divergence, and crosstalk among different signaling pathways. 7. Desensitization of receptors.
Definition
Signal transduction refers to the process that the extracellular stimuli regulate the biological functions, through membranous or intracellular receptors mediated signal cascade.
most water-soluble molecules/factors bind to cell membrane receptors and activate the signaling transduction pathway.
13
Signaling pathway via nuclear receptor
5 The mRNA is translated into a specific protein.
14
Other features: Signal Flow is not always in 1-1 fashion
Signal Receptor Transducer
Targets Response
9
Intracellular proteins
Different Kinds of intracellular proteins serve different purposes
1. Relay proteins 2. Messenger proteins 3. Adaptor proteins 4. Amplifier proteins 5. Transducer proteins 6. Bifurcation proteins 7. Integrator proteins 8. Latent gene regulatory proteins
Types of signal molecules— Lipid-soluble molecules Water-soluble molecules Gaseous molecules (NO)
Properties of signal molecules— Specificity, highly efficient, competitive Dosage-dependent, saturable Reversible, can be deactivated
5
Signal molecules
Ligand/Agonist
Proteins and peptides:
Hormones, cytokines
Bind to Amino acid derivatives: membrane Catecholamine receptors
Chemical Signal
effector. Transducers could be enzymes, adaptor, or others. Transduction is a multi-step process. 4. Effector proteins – produces a 2nd messenger such as cAMP.
These activated proteins enter the nucleus and turn on target genes .
1 The steroid
hormone testosterone passes through the plasma membrane.
2 Testosterone binds
6
1. Extracellular signal molecules: Ligand/Agonist are normally released by signal-producing cells, reach and bind to the receptor protein of target cell CONTEXT-DEPENDENT EFFECTS
Each cell is programmed to respond to a specific combinations of extracellular signal molecules, but the final read-outs are context-dependent
Fatty acid derivatives:
Prostaglandins
Extracellular molecules
Bind to
intracellular-- Steroid hormones,
receptors
Thyroxine , VD3
Physical Signal
light, wave, voice, pressure & temperature
7
2. Receptor proteins –are specific proteins, which are able to recognize and bind to corresponding ligands, and transduce signal to next signaling molecules inside of the cell.