week 6- cell signalling Flashcards
what do signal molecules bind to
receptors
what are the 4 main types of intracellular signalling
Contact-dependent, paracrine/autocrine, synaptic, and endocrine signaling
What is contact-dependent signaling?
It requires cells to be in direct membrane-membrane contact for a signal molecule to bind to a receptor on a target cell.
What is paracrine signaling?
It depends on local mediators released into the extracellular space, acting on neighboring cells.
What is autocrine signaling?
A form of paracrine signaling where the signaling cell and the target cell are the same
What is synaptic signaling?
Neurons transmit signals electrically along their axons and release neurotransmitters at synapses, often far from the cell body.
What is endocrine signaling?
it depends on endocrine cells that secrete hormones into the bloodstream for distribution throughout the body.
Where are receptors located?
On the cell surface or intracellularly.
What type of signal molecules bind to cell surface receptors?
Hydrophilic signal molecules that cannot pass through the cellular membrane.
What type of signal molecules bind to intracellular receptors?
Small, hydrophobic signal molecules that can diffuse through the plasma membrane.
Can the same signal cause different responses in different cell types?
yes
What are the three major classes of cell-surface receptors?
Ion channel-coupled receptors, G-protein-coupled receptors, and enzyme-coupled receptors.
What are ion channel-coupled receptors involved in?
Rapid signaling between neurons and electrically excitable target cells.
How do G-protein-coupled receptors (GPCRs) function?
By forming an activated receptor and G-protein complex that further activates associated enzymes.
How do enzyme-coupled receptors work?
They often rely on dimerization and interaction of cytoplasmic domains to relay signals.
What are the two types of intracellular signaling proteins that act as molecular switches?
protein kinases and GTP-binding proteins.
How do GTP-binding proteins function as molecular switches?
They exchange GDP for GTP to activate, then hydrolyze GTP to GDP to inactivate.
How does signaling by phosphorylation work?
A protein kinase adds a phosphate to the signaling protein, activating it, and a phosphatase removes it.
What are the roles of GTPase-activating proteins (GAPs) and guanine nucleotide exchange factors (GEFs)?
GAPs inactivate GTPases by hydrolyzing GTP, while GEFs activate them by facilitating the exchange of GDP for GTP.
What is often required for an appropriate cellular response?
High specificity and processing through intermediaries or second messengers.
What are some properties of signaling pathways that can vary?
Response timing, sensitivity and amplification, dynamic range and adaptation, persistence, signal processing, and integration.
What happens when two signals are needed for a cellular response?
Each signal activates different pathways that converge to fully activate a protein only when both signals are present.
What are positive and negative feedback loops?
Positive feedback amplifies signals, while negative feedback inhibits them.
What is the largest family of cell-surface receptors?
G-protein-coupled receptors (GPCRs)
what is the structure of GPCRs?
They are 7-pass transmembrane proteins.
What are some signals GPCRs respond to?
Hormones, neurotransmitters, local mediators, light photons, amino acids, and fatty acids.
How is a G-protein activated?
Binding of a molecule to a GPCR causes conformational changes, promoting GDP dissociation and GTP binding.
What are the subunits of G-proteins?
A: Alpha (⍺), beta (β), and gamma (𝛾) subunits.
What happens when the G⍺ subunit is GTP-bound?
It activates downstream signaling molecules.
: What is an example of a GPCR signaling response?
Acetylcholine-induced responses, such as decreasing heart pacemaker cell firing or promoting salivary secretion.
What does adenylyl cyclase catalyze?
The synthesis of cyclic AMP (cAMP) from ATP.
How does cAMP activate PKA?
By binding to the regulatory subunits, causing them to dissociate and activating the catalytic subunits.
What are the two types of PKAs?
Type 1 in the cytosol and Type 2 bound to membranes or microtubules
How does activated PKA affect gene transcription?
It phosphorylates the transcription factor CREB, which recruits CBP to stimulate transcription.
How do GPCRs regulate ion channels in vision?
Through phototransduction involving rhodopsin, a GPCR linked to retinal.
What happens when light is detected by rhodopsin in photoreceptors?
It causes a conformational change, activating transducin and leading to the closure of cGMP-gated Na+ channels.
How is the light signal switched off in photoreceptors?
Rhodopsin kinase phosphorylates rhodopsin, arrestin binds it, and RGS protein hydrolyzes GTP on transducin.
What is the general structure of RTKs?
Variable extracellular domain, single transmembrane domain, and variable intracellular tyrosine kinase domain.
What activates RTKs?
The binding of a signal molecule causes dimerization and phosphorylation of tyrosine residues
What are SH domains in RTK signaling?
SH2 and SH3 domains in RTK-binding proteins that recognize phosphorylated tyrosines and bind to other proteins.
What is the role of Ras GTPases in RTK signaling?
They are recruited to active RTKs and activate intracellular signaling cascades.
How is Ras activated by RTKs?
RTK binds Grb2, which binds Sos, a GEF that activates Ras by exchanging GDP for
What is required for RTK activation following the binding of the signal molecule?
Receptor dimerization and phosphorylation.
What are SH2 and SH3 domains in RTK-binding proteins?
SH2 domains bind activated phospho-tyrosines on the receptor, and SH3 domains bind domains on other intracellular proteins
What is the Ras superfamily of GTPases involved in?
Relaying signals from RTKs and various cellular processes such as cell movement, intracellular traffic, and nuclear transport.
What are the steps for Ras activation by RTKs?
- Activated RTK binds SH2 domain of Grb2.
- Grb2 binds a GEF (e.g., Sos) via its SH3 domain.
- Sos activates Ras by exchanging GDP for GTP.
What mechanisms ensure short-lived activation of Ras-GTPases?
Phosphatases remove phosphates from tyrosine residues, and Ras-GAPs hydrolyze GTP to GDP.
How do TGFβ receptors activate Smads?
The receptor complex phosphorylates receptor-activated Smads (R-Smad), which then bind co-Smad to form a trimeric Smad complex.
What does Ran GTPase control?
Nuclear transport
What triggers receptor dimerization in RTKs?
The binding of a signal molecule to the extracellular domain of the RTK.
