Test ch 16 learning objectives Flashcards
Why do cells need to communicate?
Coordinate functions such as growth, differentiation, and metabolism.
Respond to environmental changes, like stress or nutrient availability.
Maintain homeostasis by regulating internal conditions.
Support development, ensuring proper tissue formation and organization.
Trigger immune responses and cell repair mechanisms.
Types of signaling
- Endocrine signaling: Hormones travel through the bloodstream to distant target cells (e.g., insulin regulates blood glucose levels).
- Paracrine signaling: Local signaling where molecules act on nearby cells (e.g., growth factors in wound healing).
- Neuronal signaling: Neurotransmitters transmit signals across synapses (e.g., acetylcholine in muscle contraction).
- Contact-dependent signaling: Direct cell-to-cell contact via membrane-bound molecules (e.g., Delta-Notch signaling in development).
Receptors and Signal Structure
Cell-surface receptors: Bind hydrophilic molecules that cannot cross membranes (e.g., peptide hormones like insulin).
Intracellular receptors: Bind small, hydrophobic molecules that diffuse through the membrane (e.g., steroid hormones, NO).
Receptor specificity: Only cells with the correct receptor respond to a signal (e.g., only insulin-sensitive cells react to insulin).
What is a signaling cascade?
A signaling cascade is a chain of molecular events triggered by a signal.
A series of molecular interactions that transmits and amplifies a signal. Functions include:
Amplification of the signal to enhance response.
Regulation through positive and negative feedback loops.
Diversity in responses from a single signal.
Signal Amplification and key steps:
Amplification occurs when one molecule activates multiple downstream targets (e.g., cAMP in GPCR pathways).
Amplification occurs at multiple steps, including:
Enzyme activation (e.g., adenylyl cyclase producing many cAMP molecules).
Second messengers: One activated enzyme produces many molecules (e.g., cAMP, Ca²⁺).
Kinase cascades: One kinase activates multiple downstream proteins (e.g., MAP kinase).
G-protein signaling: A single receptor can activate multiple G-proteins.
Molecular switches
Molecular switches regulate signal transduction by turning pathways on or off.
GTP-binding proteins (G-proteins, Ras): Active when bound to GTP, inactive when hydrolyzed to GDP.
Phosphorylation (Kinases vs. Phosphatases): Kinases add phosphates (activate), phosphatases remove them (deactivate).
Why is signal deactivation important?
Prevents overstimulation, ensuring responses stop when no longer needed.
Examples of deactivation:
GTP hydrolysis turns off G-proteins.
Phosphatases deactivate kinases.
Receptor internalization removes active receptors from the membrane.
Without deactivation: Uncontrolled signaling → diseases like cancer.
How steroid hormones work?
Hydrophobic molecules (e.g., cortisol, testosterone).
Diffuse across the membrane and bind intracellular receptors that function as transcription factors.
Receptor-hormone complex enters the nucleus and directly regulates gene expression by binding to DNA to regulate gene expression
Slow but long-lasting effects (e.g., puberty hormones).
Slow vs Fast Responses
Fast (< seconds to minutes): Modify existing proteins (e.g., ion channel opening, enzyme activation).
Slow (minutes to hours): Involve gene expression changes (e.g., steroid hormone signaling).
How Nitric Oxide Works
Gas molecule that diffuses across membranes. It is a gas that diffuses into target cells.
Activates guanylyl cyclase to produce cGMP, leading to smooth muscle relaxation (vasodilation).
Important in regulating blood pressure.
Paracrine signaling (short-lived, only affects nearby cells).
G-protein Activation and Deactivation
1.Signal binds GPCR, changing its shape.
- GPCR activates G-protein by exchanging GDP for GTP.
- Activated G-protein splits into α and βγ subunits, triggering pathways.
- Deactivation: GTP hydrolysis converts GTP → GDP, inactivating the G-protein.
GPCR-Stimulated Signaling Pathways
- Ion Channel Pathway:
-G-protein regulates ion channels (e.g., K⁺ channels in heart cells). - Adenylyl Cyclase → cAMP→ PKA Pathway:
-Adenylyl cyclase produces cAMP.
-cAMP activates PKA, which regulates metabolism, transcription, etc.
3.Phospholipase C → DAG & IP3→ Ca²⁺ release Pathway:
-Phospholipase C cleaves PIP2 into DAG & IP3.
-IP3 releases Ca²⁺, while DAG activates PKC.
Second Messengers and Their Role
cAMP: Activates PKA.
IP3: Releases Ca²⁺ from ER.
DAG: Activates PKC.
Ca²⁺: Activates proteins like calmodulin.
IP3/DAG (triggers Ca²⁺ release, PKC activation).
Comparing Adenylyl Cyclase Vs. Phospholipase C
Function of Calmodulin
Calmodulin is in the cytosol of all eukaryotic cells
When Ca2+ binds to calmodulin it changes the shape of calmodulin. This activates CaM-Kinase
Binds Ca²⁺ to activate downstream targets.
Regulates kinases (CaM-kinase) and enzymes.
Important in muscle contraction, metabolism, and gene expression.
RTK (Receptor tyrosine kinase) and Ras Signaling
Ligand binds RTK, causing dimerization.
Autophosphorylation of tyrosines occurs and recruits adaptor proteins
Activates Ras by exchanging GDP for GTP.
Ras triggers MAPK cascade → gene expression changes.
look on slide 45
GPCR vs. RTK Comparison
Comparing Ras vs. G-proteins
look this up
How changes in Pathways Affect outcomes
-Hyperactive Ras → uncontrolled growth → cancer.
-Defective GPCR → hormonal imbalances, heart issues.
-Phospholipase C mutation → impaired Ca²⁺ signaling.
Adenylyl Cyclase Blocked → No cAMP, PKA remains inactive.
Phospholipase C Inhibited → No IP3/DAG, Ca²⁺ signaling disrupted.
TK Mutation → Ras stays active, leading to uncontrolled cell growth (cancer risk).
Second Messenger
- Small intracellular signaling molecule
- produced in large numbers (amplifies signal)
- Rapidly diffuses away from source to cause response
- Rapidly deactivated or removed
Examples of second messengers:
- cAMP, cGMP
- inositoal triphosphate (IP3)
- Calcium (Ca++)
