Cell signaling Flashcards
What are the basic requirements for signal transduction?
Signaling cell
Extracellular ligand
Target cell
Receptor
What are the three signaling types?
Endocrine
Paracrine
Autocrine
What is endocrine signaling?
Signaling molecules travel through blood stream to distant target cells
What is paracrine signaling and its two subtypes?
Signaling of nearby cells
Juxtacrine
Synaptic
What is juxtacrine signaling?
Signaling molecule is connected to signaling cell while still acting on target cell
What is synaptic signaling?
AP release NTs on nearby cells
What is autocrine signaling?
The signaling cell is also the target cell
What affects can signaling induce in a cell?
Survival
Proliferation
Differentiation
Apoptosis
Decreased rate of firing
Secretion
Contraction
What are hormones and their function?
Chemical messengers
Regulate physiological processes
What are the two classifications of hormones?
Hydrophilic
Lipophilic
What are three types of lipophilic hormones and where are their receptors located?
Steroid hormones
Thyroid hormones
Retinoic acid
In the cell - either in cytosol or nucleus
What are steroid hormones derived from?
Cholesterol
How do steroid hormones move through the blood stream?
They use a carrier protein
Where are steroid hormones synthesized and when are the released?
Synthesized on sER and released immediately
What is the precursor for thyroid hormones and what type of molecule is it?
Thyroglobulin, a large glycoprotein
Where are thyroid hormones synthesized and how do they travel through circulation?
Thyroid gland
Carrier proteins
What is retinoic acid derived from and where?
Retinol in cytosol
What are types of hydrophilic hormones and where do they bind?
AAs, peptides, proteins
Plasma membrane receptors
What are the three major classifications of cell surface receptors?
Ion-channel coupled
G-protein coupled
Enzyme coupled
What is R1 and what are its main parts?
Ligand-gated ion channel
Ionotropic receptor
Transmembrane protein with ligand binding site and pore
What is R2 and what does it rely on?
G-protein couple
Seven-membrane receptor
Relies on second messengers to give intracellular signals
What are the 3 G-proteins and what do they act on?
Gs - activates adenylyl cyclase
Gi - inhibits adenylyl cyclase
Gq - activates phospholipase C
What are the steps of GCPR-Gs signaling and what is its final product?
Ligand binds to transmembrane receptor which causes it to change shape and interact with membrane bound Gs-protein. Gs protein releases GDP and binds GTP. Alpha subunit of G-protein coupled with GTP is released, which can then bind to adenylyl cyclase to activate it. Adenylyl cyclase breaks down ATP into cAMP and PPi. PPi is used to make PKA.
Final product is PKA (protein kinase A)
What are the steps of GPCR-Gi signaling and its product?
Ligand binds to transmembrane receptor, which changes conformation to bind to Gi. This causes GDP to be released from G-protein and GTP to bind instead. Alpha subunit with GTP is released from G-protein, which binds to adenylyl cyclase to inhibit its function
Production of PKA is stopped
What are the steps of GCPR-Gq signaling and its product?
Hormone binds to transmembrane receptor which causes it to change conformation to bind to G-protein. This causes G-protein to lose GDP and bind GTP. Alpha subunit plus GTP is released, which then binds to phospholipase C to activate it. Phospholipase C cleaves PIP2 into IP3 and DAG. IP3 binds to receptor on ER to signal release of Ca ions. DAG and Ca ions activate PKC. PKC phosphorylates proteins for cellular responses.
PKC that phosphorylates cellular proteins
What are two enzyme couple receptors?
Receptor tyrosine kinase (RTK)
Receptor serine-threonine kinase
How RTK activated generally?
Inactive RTK transmembrane protein bound in extracellular environment. RTK is phosphorylated - cooperativity affect. Intracellular proteins bind to phosphorylated tyrosine. Activated signaling proteins have various effects in cell.
What are the three RTK pathways?
PI3-K
Ras/MPK
PLC
What signaling molecules use RTK pathways?
Insulin
Some growth hormones
What are the steps of the PI3-K (A1) pathway and its product?
Ligand binds to transmembrane receptor. Receptor dimerizes and is phosphorylated (Ys). Activated receptor recruits signal transducers, like IRS1. Formation of binding sites with SH2 domains to bind PI3K. PI3K phosphorylates PIP2 into PIP3. PIP3 phosphorylates Akt (PKB) to activate it. This causes phosphorylation cascade downstream. This causes GLUT4 to translocate to membrane.
GLUT4 in membrane
What are the steps of the RAS/MAPK pathway and its product?
Transmembrane RTKs are phosphorylated and recruit signal transducers. Formation of binding sites with SH2 domains, SHC. SHC binds to Grb2, which binds to SOS. That complex binds to RAS, which allows it to bind GTP. RAS with GTP stimulates downstream effectors, GTP to GDP. This leads to activation of MAP kinases ERK1 and ERK2. ERK enters nucleus. It phosphorylates and activates transcription factors for growth and proliferation. Can affect gene differentiation
ERK enters nucleus and activates transcription factors.
What are the steps of the PLC (A3) pathway and its product?
Activated RTKs recruit signal transducers. Bind and phosphorylate substrates with SH2 domains - PLC-gamma. This stimulates phospholipase activity. PLC cleaves PIP2 into IP3 and DAG. IP3 binds to receptor on ER to cause release of Ca ions. Ca and DAG activate PKC. PKC activates transcription factors.
PKC that activates transcription factors.
What are the steps of the receptor serine threonine kinase (R3B) pathway and its products?
TGF-beta binds to receptor. Activates phosphorylation of serine or threonine. They will bind Smad proteins and activate them. Smads are transcription regulators and will enter nucleus.
Activated Smads - transcription regulators
How does positive feedback relate to transmembrane receptor proteins.
When a transmembrane protein is active and one substrate binds, it increases the likelihood of additional substrates to bind
What are factors that govern receptor activation?
Level of circulating ligand
Relative number of receptors
Receptor affinity
Why would receptors be up-regulated?
In response to reduced level of ligand
Increase transcription and translation
Decrease degradation of receptors.
Activation of receptor
Why would a receptor be down-regulated?
Reduce transcription and translation
Increase degradation of receptors
What is desensitization and when does it occur?
Reduced response to same ligand or same concentration of ligand - no response over time - will require greater ligand concentration to respond
Can occur after prolonged exposure to ligand, receptor endocytosis, receptor down-regulation, and receptor inactivation
What is an agonist?
Binds to receptor and activates it the same way as a ligand
What is an antogonist?
Binds to receptor to prevent ligand binding, thus stopping the pathway
