Cell Signaling Flashcards
(50 cards)
What are the four main signal transduction pathways that we discussed? What makes one
pathway especially different from the others?
- GPCRs
- RTKs
- single-pass (one transmembrane segment)
- Enzymatic activity: tyrosine kinase
- Binding of ligand causes each receptor to dimerize
- Dimer formation causes Cross phosphorylation (phosphorylation occurs on tyrosines)
- 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 - signal molecules diffuse locally
- Contact-dependent (e.g., embryonic development)
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? What are some examples?
Second messengers - amplify and spread intracellular signal
Examples:
- cAMP
- IP3
- Ca2+
- DAG
What are effector molecules?
Proteins that change behavior of cell; have direct effect on behavior of target cell
What type of signaling events are slow? Fast? What are the explanations for this?
Slow:
- Cell growth/division
- Explanation: changes in gene expression
Fast:
- Skeletal muscle contraction
- Salivary gland secretion
- Metabolism
- Explanation: Signal affects activity of proteins already present inside target cell; do not involve changes in gene expression
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.
Different type of receptor protein
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)
