Signal Transmission Flashcards
What is cell signaling?
The ability of cells to receive and act on signals from their environment is fundamental to life
How do cells respond to signals of the environment?
Cells respond to signals from their environment by regulating their activities and the activities of other cells
Regulation of cellular processes involve regulation of metabolism and gene expression
What is metabolic regulation?
Is the balanced of the production of energy and synthesis of end products to the metabolic demands of the cell
What is the importance of metabolic regulation?
- It ensures a constant supply of energy and is critical to survival in a changing environment
- An effective communication system is needed to coordinate the metabolic activities of cells
Metabolic regulation depends on signals inform the cells, what 2 ways can this be done?
A. Intracellular (signals originate within cells)
B. Intercellular (between cells)
Most cells are ____________ in nature
Chemical
Give a brief summary of intracellular signals
- Signaling via secreted molecules. Most important route for metabolism
- Signaling via cell surface molecules
- Signaling via gap junctions
Give an overview of signal transduction
- Synthesis and release of signaling molecule (first signal) in response to a stimulus
- The signaling molecule is transported to target cell where it binds to a receptor protein
- Activated receptor generates intracellular signals that result in an appropriate response
- Termination of response
What is the function of receptors in signal transduction ?
They bind to extracellular signal and transmits the signal into the cell by promoting activation or synthesis of intracellular molecules
These then lead to target proteins and a cellular proteins
List the general features of signaling transduction
- Specificity
- Amplification
- Desensitization/adaptation
- Integration
Describe the specificity of signaling transduction.
Signal molecule fits binding site on its complementary receptor; other signals do not fit
Describe the amplification of signal transduction
When enzymes activate enzymes, the number of affected molecules increases geometrically in an enzyme cascade
Describe the desensitization/adaptation of signal transduction
Receptor activation triggers a feedback circuit that shuts off the receptor or removes it from the cell surface
Describe integration of signal transduction
When two signals have opposite effects on a metabolic characteristic such as the concentration of a second messenger X, or the membrane potential Vm, the regulatory outcome results from the integrated input from both receptors
How do intracellular receptors work?
- Cytoplasmic receptor can bind to the signal molecule(ligand) then translocations to the nucleus
- Or receptor can be found in the nucleus bound to the DNA or proteins.
- Usually bind to steroid hormones or other lipophilic signal molecules(thyroid hormone)
What are the types of signal transduction pathways?
- Steroid receptor
- Gated ion channel
- Enzyme receptor(catalytic)
- G-protein coupled receptor(GCPR)
Give the general Features of steroid receptor transduction pathways
- Steroid binds to receptor in cytoplasm or nucleus of cells
- Act as ligand-activated transcription factor
- Activated receptor binds to DNA and alters the rate of gene transcription
What are examples of steroid receptor
Androgen hormone receptor
Progesterone receptor
Give the general features of the Gated ion channel
Binding opens or closes an ion channel
Give examples of gated ion channel receptors
Nichotonic ACh receptors of muscle or nerve, y-aminobutyric acid (GABA), Glycine receptors in the CNS
Give the general features of enzyme receptor (catalytic)
Catalyzes production of a intra-signaling molecule
Give an example of an enzyme receptor (catalytic)
Tyrosine kinase receptor
Give the general features of G-protein Coupled receptor(GPCR)
G-proteins activate enzymes that produce second messengers
Give an example of G-protein Coupled Receptor(GPCR)
Epinephrine/Norepinephrine receptor(beta and alpha adrenergic)
How long does steroid receptor mechanism takes?
May take hours or days(slow)
Explain the steroid mechanism of transduction
- Hormone(H), carried to the target tissue on serum binding proteins diffuses across the plasma membrane and binds to its specific receptor protein (Rec) in the nucleus
- Hormone binding changes the conformation of it forms homozygous or heterodimers with other hormone receptor complexes and binds to specific regulatory regions called hormone response elements (HREs) in the DNA adjacent to specific genes
- Binding regulated transcription of the adjacent gene(s), increasing or decreasing the rate of mRNA formation
- Altered levels of the hormone-related gene product produce the cellular response to the hormone
Describe gated ion channel signal transduction
Receptor linked to ligand or voltage-gated ion channel
Binding of neurotransmitter causes channel to open or close
Results in rush of ions through ion channel altering membrane potential promoting or inhibiting nerve impulse transmission
Describe enzymatic (catalytic) receptor function
- Transmembrane catalytic receptors that have enzymatic activity as part of their structure
- Enzyme is a tyrosine- specific protein kinase(adds a phosphate to specific tyrosine residues)
- Contain an extracellular domain for binding ligand and an intracellular domain with tyrosine kinase activity
Describe insulin receptors as enzyme (catalytic) receptors
Insulin receptor in which binding of ligand —> ATP cleavage, autophosphorylation and phosphorylation of specific tyrosine residues in target proteins —> signaling cascade and response activation
What are the importance of the extracellular domain of G-coupled Protein receptors?
The extracellular domain contains the binding site for a ligand (a hormone or neurotransmitters)
Describe the importance of the intracellular domains in G-coupled protein receptors
Intracellular domain that interacts with G-proteins
Briefly describe GPCRs signal transduction
- The hormone or neurotransmitter, is the first messenger that binds to the plasma membrane receptor
- Receptor activates a G-protein, that stimulates an effector enzyme to produce a second messenger
Example: Adenylyl Cyclades system(cAMP)
Phosphoinositide system(IP3, DAG and Ca2+)
What are hetero-trimeric G proteins?
- Intracellular signaling proteins that can bind to and hydrolyzed GTP(guanosine triphosphate )
- Composed of three subunits a, B and y
- Three subunits associate and a subunit binds GDP when inactive
How are Hetero-trimeric G proteins activated and inactivated?
- Activated by ligand binding to GPCRs
- a subunit exchanges GDP for GTP and dissociates from B and y subunits when active
- GTPase activity hydrolyzes GTP and G-protein reverts to inactivate state
Describe intracellular second messengers
- small soluble intracellular molecules produced in response to activation of a cell surface receptor
- they trigger a cascade of intracellular events(enzyme activation, inhibition) that activates an appropriate cellular response
Give examples of intracellular second messengers
- cAMP
- IP3, DAG, Ca2+
- cGMP
- NO(nitric oxide)
Describe the Adenylyl Cyclades System of GPCR signaling systems
Second messengers is cAMP
- Binding of hormone to receptor
- Activation of Gsa
- Gsa protein activates adenylyl Cyclase
- Adenylyl cyclase synthesizes cAMP from ATP
- cAMP activates Protein kinase A
- Protein kinase A phosphorylates target proteins resulting in cellular responses
- Phosphodiesterase hydrolysis cAMP to 5’-AMP and terminates signal
Contrast the signal(first messenger) Adenylyl cyclase system and phosphoinositide (GPCR signaling systems)
Adenylyl cyclase system-Glucagon, Epinephrine/Norepinephrine
Phosphoinositide system- Epinephrine/norepinephrine
Contrast the receptors of Adenylyl cyclase system and phosphoinositide system (GPCR)
Adenylyl Cyclase systems - Glucagon receptor, B-adrenergic receptor
Phosphoinositide system- A-adrenergic receptor
Contrast the G proteins in Adenylyl Cyclase and Phosphoinositide systems
Adenylyl cyclase - Gs
Phosphoinositide- Gq
Contrast the effector enzymes of Adenylyl cyclase and phosphoinositide systems (GCPR signaling )
Adenylyl cyclase effector enzyme - Adenylyl cyclase
Phosphoinositide effector enzyme- Phospholipase C
Contrast second messengers between Adenylyl cyclase and phosphoinositide (GPCR systems)
Adenylyl cyclase- cAMP
Phosphoinositide- IP3, DAG, Ca 2+
Contrast the Ser/Thr kinase between Adenylyl cyclase and phosphoinositide
Adenylyl Cyclase- protein kinase A
Phosphoinositide- Protein kinase C
What is phosphotidylinositol 4, 5-bis-phosphate (PIP2)?
Phospholipid found in the inner leaflet of the plasma membrane
What role does Phosphatiylinositol-4,5-is-phosphate (PIP2)play in the phosphoinositide system?
- Phospholipase C cleaves PIP2 to generate IP3 and DAG
- IP3 is soluble and moves through cytoplasm
- DAG is hydrophobic and remains in the plasma membrane
(Primary messenger)
Give the process phosphoinositide system after the second messenger
- second messengers produced are IP3, DAG and Ca2+
1. Gqa activates Phospholipase C (PLC)
2. PLC cleaves PIP2 to IP3 and DAG
3. IP3 causes Ca2+ release from ER
4. DAG activates Protein kinase C
5. Protein kinase C phosphorylates substrate proteins resulting in cellular responses
6. Protein kinase C requires DAG, Ca2+ and phospholipids for maximal activity
What are the sites of signal termination?
- removal of signaling molecule
- removal of receptor
- inactivation of signal transduction events
Give examples of signal termination
- degradation of insulin by liver
- Intrinsic GTPase activity of G-proteins
- Hydrolysis of cAMP by phosphodiesterase
- Reversal of phosphorylation effects by phosphatases
