Block 3 - second messenger systems (L3-4) Flashcards
Cell-cell communication can occur via…
endocrine, paracrine, autocrine chemical messengers
direct transfer of factors via protein pores connecting the cytoplasm of neighboring cells
Cell signaling can be initiated by…
- secretion of chemical messengers
- arrival of external signals (odorants, tastants, or xenobiotics)
- metabolites and ions
The most common “molecular switch” is…
phosphorylation
Specific kinases phosphorylate…
tyrosine, serine, and threonine amino acids
What are kinases and phosphatases?
kinases - phosphorylate
phosphatases - dephosphorylate
Phosphorylation can —– an enzyme’s catalytic activity
increase or decrease
What are the 4 types of cellular receptors?
ligand gates ion channels
G protein couples receptors
catalytic receptors
nuclear receptors
How do ligand gated ion channels work? What are 2 examples?
- integral membrane proteins interact with an ion channel to modify flux across the channel (the channel can be part of the receptor)
- ion acts as the initial second messenger
- Nicotinic ACh receptors (muscles get signals from the nervous system to contract)
- ATP-sensitive K+ channels (insulin secretion from pancreatic B cells)
How do GPCRs work? What are 2 examples?
- activate a heterotrimeric complex G-protein (GTP-binding protein)
- modulates an enzyme or ion channel
- product of the enzymatic activity (or the ion) acts as the initial second messenger
- a and B adrenergic receptors
- glucagon receptors
How do catalytic receptors work? What is an example?
- activate enzymatic activity of the receptor
OR - initiate a series of events that activate an enzymatic complex
- the initial second messenger is the product of the activated enzyme via phosphorylation of the substrate
- insulin receptor
How do nuclear receptors work?
- in the cytoplasm or nucleus
- act as transcription factors to modulate the transcription of specific genes
- alter protein expression of the gene products
- no second messengers
What are the 6 steps to initiate a signaling event by a plasma membrane receptor?
- recognition - ligand binds receptor
- transduction - ligand binding induces conformational change, produces a second messenger
- transmission - second messenger interacts with intracellular effectors
- modulation of the effector - activates a protein kinase or phosphatase that changes the phos. state of a downstream target and alters its functionality
- response - modified cellular function in highly specific ways
- termination - feedback mechanisms stop the signaling events and return cellular function to a basal state
What is amplification?
increased production of a second messenger at each step of a multi-step signaling cascade
leads to enhanced activation of a cellular process by several orders of magnitude
What types of receptors transduce information from extracellular chemical messengers?
ligand gated ion channels
g protein couples receptors
catalytic receptors
The ligand gated ion channels in skeletal muscle are called…
nicotinic acetylcholine receptors
When a ligand binds a g protien-coupled receptor, what happens?
GDP is exchanged for GTP
G protein dissociates from the receptor and ligand releases
alpha subunit dissociates from By, so they can each interact with their appropriate effectors
GTP hydrolysis causes reassembly of the g protein
G proteins can bind to 4 kinds of effectors:
- adenylate cyclases
- phosphodiesterases (PDEs)
- phospholipase C (PLC)
- Ca++ channels
In what ways can G proteins interact with adenylate cyclase?
- Gs activates AC, increasing cAMP and increasing PKA activity
- Gi inactivates AC, lowering cAMP and decreasing PKA activity
How can G proteins interact with phosphodiesterases (PDEs)?
- Gt activates PDE, breaks down cGMP, inactivating cGMP-dependent ion channels
How can G proteins interact with phospholipase C (PLC)?
- Gq activates PLC, cleaves PIP2 into DAG and IP3
- DAG activates protein kinase C (PKC)
- IP3 stimulates Ca++ release from the ER
What are the main types of catalytic receptors?
- receptor guanylate cyclases
- receptor serine threonine kinases
- receptor tyrosine kinases
- tyrosine kinase-associated receptors
- receptor tyrosine phosphatases
What do receptor guanylate cyclases do?
produce cGMP from GTP (ex: ANP receptors)
What do receptor serine-threonine kinases do?
phosphorylate serine and threonine (ex: TGF-B receptors)
What do receptor tyrosine kinases do?
phosphorylate tyrosine (ex: NGF receptors)
What do tyrosine kinase-associated receptors do?
interact with and activate cytosolic tyrosine kinases (ex: growth hormone receptors)
What do receptor tyrosine phosphatases do?
dephosphorylate tyrosine (ex: CD45)
The insulin receptor is a type of…
catalytic receptor, specifically a tyrosine kinase receptor
Describe the mechanism for a tyrosine kinase receptor in 5 steps
- binding: single exofacial subunit binds ligand, causing dimerization of two receptors (insulin is pre-dimerized)
- activation: conformational change causes auto-phosphorylation of tyrosine residues and activation of the receptor complex, which further increases in receptor tyrosine kinase activity
- enhancing: enhanced tyrosine phosphorylation of cytosolic proteins
- effector modification: activation of downstream effectors modifies cell function
- termination: receptor activity ceases when 1) ligand receptor complex is internalized or 2) the action of a specific phosphatase dephosphorylates the receptor
