Cell Signaling Flashcards
What are the three mains steps of cell signaling?
- Reception: Ligand binds with receptor
- Transduction: Signaling cascade
- Cell Response: Response within the cell
What are the 4 main classes of receptors?
- Ion Channels
- G-Protein Coupled Receptors (GPCRs)
- Kinase or Kinase Associated Receptors
- Intracellular Receptors
Ion Channel
- Binding of ligand allow ions to cross membrane, can:
- Changes membrane potential
- Activate signal proteins or channels
- Release intracellular calcium
- Examples:
- Acetylcholine receptors on muscle
- GABA A receptors
G-Protein Coupled Receptors are ____-transdomain receptors
G-Protein Coupled Receptors are 7-transdomain receptors
G-Protein Coupled Receptors (GPCRs)
Mechanism of Action
- Ligand binding activates associated G protein (trimers with a, b, and y components)
- When activated the alpha component binds GTP, dissociates, and activates an enzyme
What are the three classes of G-protein alpha subunits
q
i
s
GPCR: Gs
Mechanism of Action
Examples
Mechanism of Action (s stimulates PKA):
- S activates adenylate cyclase
- Adenylate cyclase produces cAMP
- cAMP activates Protein Kinase A (PKA)
Examples of Gs GPCRs:
- Serotonin R 4, 6, 7
- Histamine H2 R
- Prostoglandin I2 R
- Calcitonin R
GPCR: Gi
Mechanism of Action
Examples
Mechanism of Action (i inhibits PKA):
- i inhibits adenylate cyclase
- Leads to decrease of cAMP
- Leads to decreased activity of Protein Kinase A (PKA)
Examples:
- Norepinephrine a2 R
- Adenosine A2 R
- Glutamate R 2-3, 6, 8
- GABA B Receptor
GPCR: Gq
Mechanism of Action
Examples
Mechanism of Action:
- q activates PLC
- PLC cleaves PIP2 to make IP3 and DAG
- IP3 releases intracellular Ca2+ from the ER
- DAG and Ca2+ activate Protein Kinase C (PKC)
Examples:
- Norepinephrine a1 R
- Anngiotensin II R (AT2)
- Vasopressin R (V1)
Receptor Tyrosine Kinase (RTK)
Mechanism of Action
Examples
Mechanisms of Action:
- Ligand binds –> receptor dimerizes
- Receptors phosphorylate eachother at Tyrosine residues
- Recruits SH proteins:
- Enzymes: Src, PLC
- Adaptors: SOS
- SOS activates the RAS Enzyme
- RAS activates RAF which is a MAPKKK that acts in the MAP Kinase Cascade
Examples:
- Insulin
- VEGF and FGF
- BDNF
MAP Kinase Cascade
- Series of kinases downstream of RTKs
- Phosphorylation acts as an on/off switch
- RAS activates RAF
- RAF is a MAPKKK that activates MEK which is a MAPKK
- MEK activates ERK which is a MAPK
- ERK acts on multiple targets
RTK Example: Insulin Receptor
Mechanism of Action
Cell Response
Mechanism of Action:
- Receptor is a tetramer at start (2a and 2b)
- Insulin binds –> Receptors phosphorylate eachother at Tyrosine residues
- Receptors phosphorylate IRS and SHC proteins
- IRS activates enzyme to make PIP3
- PIP3 works with a kinase to activate AKT
- Additionally SHC leads to activation of RAF
Cell Response:
- Glucose transport proteins (GLUTs) are expressed on cell membrane
- Glycogen storage increases
- Protein synthesis increases
Serine-Threonine Kinase
Mechanism of Action
Examples
Mechanism of Action
- Ligand binds –> Receptor dimerizes
- Receptors phosphorylate each otheron serine or threonine residues
- SMAD binds and gets phosphorylated
- SMAD binds co-SMAD, and this SMAD complex enters the nucleus and changes gene expression
Examples:
- TGF-B
- Tumor Necrosis Factor
- BMP
JAK-STAT
Mechanisms of Action
Examples
Mechanisms of Action:
- Ligand binds –> receptor dimerizes
- JAK proteins bind and phosphorylate each other and the receptor
- STAT proteins bind and get phosphorylated
- STATs dimerize, enter nucleus, and change gene expression
Examples:
- TINs: erythropoietin, thrombopoietin, prolactin
- TERs: interluekins, interferons (cytokines)
- Growth Hormone
- GM-CSF
Intracellular Receptors
Mechanism of Action
Examples
Mechanisms of Action
- Ligand diffuses across the membrane (hydrophobic)
- Binds to receptor inside the cell
- Translocated to nucleus to change gene expression
Examples
- Cortisol
- Testosterone and Estrogen
- Aldosterone and Vitamin D
