Cell Signaling - IV

Chapter 16 - Cell Signaling

extracellular; intracellular

Cells convert ________ signals into an ________ signal.

• e.g., like a phone that recieves a signal and has an output

Endocrine

secreted at a distal part (liver) and dispersed throughout the body thru blood

Paracrine

released by a cell to act as a local mediator for nearby cells

Neuronal

electrical signals that travel between two neurons

Contact dependent

membrane bound signal molecule between two adjacent cells

Extracellular

Intracellular or extracellular?

the signal is:

• large

• hydrophilic (charged)

• cannot cross the membrane → receptor is outside

Intracellular

Intracellular or extracellular?

the signal is:

• small

• hydrophobic (uncharged)

• cross the membrane → receptor is inside

Small, nonpolar molecules

Which one diffuses more easily?

a.) Small, nonpolar molecules

b.) large, polar molecules

large, polar molecules

Which one crosses very slowly?

a.) Small, nonpolar molecules

b.) large, polar molecules

size; solubility

The rate of solute diffusion across a protein-free artificial lipid bilayer depends on the solute’s _______ and ________.

Cortisol

• diffuses across the plasma membrane

• binds a cytosolic receptor because it is lipid-soluble

hormone-receptor

The ______-_______ complex translocates to the nucleus through nuclear pores.

• in intracellular receptors

transcription

In the nucleus, the activated receptor-cortisol complex binds to the regulatory region of the target gene and activates __________.

• acts as a _______ regulator, altering gene expression in response to stress.

Fast responses

Fast or slow cell signaling response?

• may not need changes to gene expression

  • e.g., movement or secretion

Slow responses

Fast or slow cell signaling responses?

• require many genes to be expressed and many new proteins to be made

  • e.g., differentiation, growth or division

cell-surface

Extracellular signals trigger intracellular signaling pathways by binding ____-________ receptors.

extracellular; intracellular

Cell-surface receptors relay _______ signals via ________ signaling pathways

effector proteins

proteins that are altered to change the cell’s behavior

signaling molecules

Intracellular Signaling pathways involve cascades of ______ _______ (proteins or small messengers) that relay and amplify the signal.

Intracellular

________ signaling proteins relay, amplify, and distribute signals, allowing them to spread and strengthen within the cell.

Cell-surface receptors

transduce extracellular signals into intracellular signals, initiating one or more signaling pathways.

feedback

Intracellular signaling proteins can also integrate multiple signals and modulate responses via ________, fine-tuning the cell’s behavior.

Feedback loops

______ ______ fine-tune cellular responses, ensuring signals are amplified, dampened, or oscillated as needed for proper cell function. There are two kinds

positive feedback

downstream protein (e.g., protein Y) enhances the activity of the protein that activated it, potentially triggering rapid or “explosive” responses like cell division.

negative feedback

downstream protein inhibits the protein that activated it, creating oscillations in activity similar to predator–prey dynamics.

cell memory

What’s an example of positive feedback within the cell?

• necessary for a proliferating cell to maintain its identity; must be remembered by each daughter cell

Phosphorylation

a protein kinase may add a phosphate group and a protein phosphatase may remove a phosphate group.

• doesn’t necessarily mean activation or deactivation

molecular switch

Some intracellular signaling proteins act as a _______ ______ to turn themselves (or others) on or off.

• These activities could be regulated by processes such as phosphorylation.

GTP-binding protein

They toggle between active and inactive state based on whether they have GTP or GDP bound to them.

• They also have intrinsic GTPase activity (removing GTP) to stop themselves when needed

GEFs (guanine nucleotide exchange factors)

activate GTPases by promoting GDP → GTP exchange.

GAPs (GTPase-activating proteins)

inactivate GTPases by stimulating GTP → GDP.

GTPases

• function as molecular switches

• cycling between:

  • active (GTP-bound) and inactive (GDP-bound) states.

Ion-channel-coupled receptors

• opens in response to binding an extracellular signal molecule.

• These channels are also called transmitter-gated ion channels.

• Change the permeability of the plasma membrane to selected ions 

GPCRs

Signal binds → G protein activated → enzyme/ion channel turned on/off

G protein

When a GPCR binds an extracellular signal, it activates a ___ ______ inside the cell.
The G protein then turns an enzyme or ion channel on or off in the cell membrane.

cytosolic

When a G-protein-coupled receptor binds its extracellular signal molecule, the activated receptor signals to a trimeric G protein on the _______ side of the plasma membrane, which then turns on (or off) an enzyme (or an ion channel) in the same membrane. 

Enzyme-coupled receptors

Signal binds → enzyme inside cell turns on (built-in or attached)

enzyme; associated

Many enzyme-coupled receptors have their own _____ activity (left), while others rely on an enzyme that becomes _________ with the activated receptor (right).

Covalent modifications

can regulate protein location and interactions, not just activity.

• e.g., phosphorylation

Phosphorylation

can create docking sites that allow other proteins to bind and form larger signaling complexes.

Receptor tyrosine kinases

phosphorylate themselves in response to extracellular signals, recruiting intracellular signaling proteins that transmit signals and alter cell behavior.

kinase

a type of enzyme that catalyzes phosphorylation

ion channels

• channels that are gated and are opened or closed briefly

• are ion-selective

diameter; shape; distribution

Ion selectivity is achieved by the _______ and _____ of the ion channel and on the ______ of the charged amino acids that line it.

Lock and key model

• The same signal molecule can induce different responses in different target cells.

• Different cell types are configured to respond to the neurotransmitter acetylcholine in different ways