Cell Signaling Flashcards
What are the four main signal transduction pathways that we discussed? What makes one
pathway especially different from the others?
- GPCRs
- RTKs
- Receptors only single-pass
- Enzymatic activity: kinase
- Binding of ligand causes each receptor to dimerize
- Dimer formation causes Cross phosphorylation
- Uses Ras (small G protein) - Steroid hormones
- do not need cell surface receptors
- go directly into membrane
- cross plasma membrane on their own
- bind nuclear receptors in cytoplasm - Notch signaling
- Activated by binding of Delta -> cleaves Notch receptor
- Cleavage releases cytosolic tail of receptor -> moves to nucleus (activates Notch-responsive genes)
Indicate types of signaling that are short range versus long range.
Short range:
- Paracrine
- Contact-dependent
Long range:
- Neuronal signaling - neurotransmitters
- Endocrine - hormones
What are some examples of signaling molecules (ligands)?
- Proteins
- Peptides
- Amino acids
- Nucleotides (e.g., cAMP)
- Steroids
- Fatty acid derivatives (hydrophobic)
- Dissolved gases (e.g., NO)
What is an autocrine signal?
Cell signals to itself
Compare and contrast cell-surface receptors and intracellular receptors.
Cell-surface receptors:
- do not transverse membrane
- signal molecule (hydrophilic)
Intracellular receptors:
- small, hydrophobic signal molecules
- primarily steroid hormones
- receptor in cytosol
- once bound to receptor, it goes into nucleus
What is the difference between immediate outcomes/responses and long time outcomes/responses?
Immediate:
- do not require gene expression
- physiological responses that require immediate attention
- e.g., adrenaline
Long time:
- requires gene expression
- associated with cell division, developmental movements of tissues
Give an example of how the same signal molecule can induce different responess in different target cells.
Acetylcholine:
- Heart pacemaker cell -> decreased rate of firing (same receptor as salivary gland cell – G-protein coupled receptor)
- Salivary gland cell -> secretion (same receptor as heart pacemaker cell – G-protein coupled receptor)
- Skeletal muscle cell -> contraction
What are the three main classes of cell-surface receptors?
- Ion-channel-coupled receptors
- G-protein-coupled receptors - activate membrane-bound, trimeric G proteins
- Enzyme-coupled receptors - either act as enzymes or associate with enzymes inside cell
Compare and contrast ECRs with GPCRs
G-protein-coupled receptors
- receptor - 7 transmembrane protein
- Trimeric G protein - alpha, beta, gamma subunit
* Beta subunit - always in connection with gamma
* Alpha subunit - has GDP nestled in pocket
* GTP associated with alpha subunit –> G protein dissociates
Enzyme-coupled receptors
- Receptors themselves have enzymatic activity
- Single-pass (one transmembrane domain)
- Functions as dimers
- Inactive - receptors far apart
- Active - receptors come together
How do trimeric G proteins function? Draw an inactive state versus an active state.
Three subunits: alpha, beta- gamma (alpha and gamma tethered to PM by lipid tails)
Inactive state: alpha subunit has GDP bound
- Alpha subunit detaches from By complex
What are second messengers, how do they form? What is the primary messenger?
Second messengers - amplify and spread intracellular signal
What are effector molecules?
What type of signaling events are slow? Fast? What are the explanations for this?
What is a molecular switch? What are two examples? How do they influence a signaling event?
Molecular switch - intracellular signaling protein that switches from an inactive to an active state
1.Phosphorylation/dephosphorylation
- GTP-binding proteins (Small G-protein) - toggle between active state (GTP bound) and inactive state (GDP bound)
What proteins regulate a molecular switch? Hint: there are two important ones.
Protein kinase and protein phosphatase
Explain how acetylcholine can slowdown heart rate, but also induce a muscle contraction.
How do G proteins shut themselves off?
Alpha subunit has intrinsic GTPase activity -> hydrolyzes bound GTP
Which is the shortest range signal transduction pathway? How does it function?
GPCR superfamily
- Rhodopsin
- Olfactory receptors in nose
- Single-celled yeast mating receptors
How does acetylcholine reduce heart rate?
Acetyhcoline binds to GPCR on surface of heart pacemaker cells
By-complex dissociates from alpha-subunit and bind K+ channel in plasma membrane, forcing it open
K+ channel allows K+ to flow out of cell
Results in a more polarized membrane making it harder to electrically activate
cAMP is synthesized by ____________ and degraded by _____________.
adenylyl cyclase; cyclic AMP phosphodiesterase
cAMP is activated by adenylyl cyclase. What switches on adeneylyl cyclase?
Activated G protein a-subunit
Adenylyl cyclase activates cAMP. What does cAMP activate?
cAMP-dependent protein kinase (PKA)
What is the function of cyclic AMP phosphodiesterase?
Degrades cAMP
clips ring from cAMP –> becomes AMP (does not have amplifying activity)
Why does caffeine act as a stimulant by blocking cAMP phosphodiesterase?
Skeletal muscle
Epinephrine signaling leads to rise in cAMP
Activated andelyly cyclase takes ATP to make cAMP
cAMP activates PKA
PKA phosphorylates (activates phosphorylase kinase)
Phosphorylase kinase activates glycogen phosphorylase - breaks down glycogen
Glycogen breakdown → increase in glucose levels
PKA also inhibits enzyme that drives glycogen synthesis
PKA
Involved in activating targeted genes
Goes into nucleus and activates transcription regulators
Move from cytosol into nucleus to phosphorylate and activate transcriptional regulators
What are two ways a response can be terminated in ECRs?
- Tyrosine phosphatases
- Get rid of ligand
Explain the role of Ras in ECRs.
Inactive: GDP is bound
Active: GTP is bound
Ras-GEF - activates Ras; encourages Ras to exchange its GDP for GTP
Ras-GAP - hydrolyzes GTP to GDP; switches Ras off
Activates MAP kinase kinase kinase
What are examples of RTKs that activate Ras?
- PDGF receptors - mediate cell proliferation in wound healing
- NGF receptors - play an important role in the development of certain vertebrate neurons
- EGF receptors - stimulate cell growth and differentiation
What are mitogens?
Extracellular signaling molecules that stimulate cell proliferation (promotes cell division/mitosis)
MAP kinase cascade
Ras -> activates MAP kinase cascade
MAP kinase kinase kinase -> phosphorylates and activates MAP kinase kinase
MAP kinase kinase - > phosphorylates and activates MAP kinase
MAP kinase phosphorylates effector proteins
What is the importance of Notch signaling?
Controls development of sensory neurons in flies
What is lateral inhibition in Notch signaling?
when a precursor cell commits to becoming a neural cell, it signals to its immediate neighbors not to do the same, and inhibited cells develop into epidermal cells instead
Explain the process of Notch signaling.
Notch is cleaved
Piece of it goes from plasma membrane and into nucleus (becomes transcriptional regulator)
The Notch receptor functions as a _____________.
Transcriptional regulator
What category of signaling is Notch signaling?
Contact-dependent signaling
What are local mediators?
Secreted molecules that act only on cells in local environment of signaling cell
What are the two types of GTP-binding proteins?
- Trimeric G proteins - relay messages from GPCRs
- Monomeric GTPases - aided by GEFs and GAPs
What are the two main types of protein kinases that operate in intracellular signaling pathways?
- Serine/threonine kinases - phosphorylate proteins on serines or threonines
- Tyrosine kinases - phosphorylate proteins on tyrosines
GEFs - promote exchange of GDP for GTP (switches protein on)
GAPs - stimulates hydrolysis of GTP to GDP (switches protein off)
Describe the common structure of GPCRs.
Polypeptide chain traverses membrane as seven alpha helices
Cytoplasmic portions of receptor bind to G protein inside cell
Where is the G protein located in relation to the GPCR?
Cytosolic side of plasma membrane
Is the trimeric G protein complex active when assembled or disassembled?
Disassembled
What are RTKs important for?
cellular growth, proliferation, differentiation, survival and development
