Cell Signaling Part 1 Flashcards by IVAN Dyan

allows bacteria to coordinate their behavior, including their motility, antibiotic production, spore formation, and sexual conjugation

Quorom sensing

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signals cells of the opposite mating type to stop proliferating and prepare to mate.

Mating factor in yeast

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Intracellular signaling pathway

Extracellular signal molecule -> receptor protein -> Intracelullar signaling molecules -> effector proteins

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Where reception of the signals depends on
at the cell surface, which bind the signal molecules

Receptor protein

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Results after the binding of the receptor

intracellular signaling pathways or system

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process the signal inside the receiving cell.

distribute them to appropriate intracelullar targets

Intracellular signaling proteins

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small chemical messenger which carry the signal to other signaling proteins

Second messengers

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the targets that lie at the end of signaling pathways

effector proteins

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Four forms of intercellular signaling

Contact-dependent
paracrine
synaptic
endocrine

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requires cells to be in direct membrane- membrane contact

Contact-dependent signaling

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depends on local mediators that are released into the extracellular space and act on neighboring cells.

Paracrine signaling

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is performed by neurons that transmit signals electrically along their axons and release neurotransmitters at chemical synapses, which are often located far away from the neuronal cell body

Synaptic signaling

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depends on endocrine cells, which secrete hormones into the bloodstream for distribution throughout the body

Endocrine signaling

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cells produce signals that they themselves respond to

Autocrine signaling

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neurons; chemical
synapses

synaptic

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high specificity of binding site of receptors

Target cell

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extracellular signal molecule

ligand

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cell responds to the signals ___

selectively

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a signal molecule often has ___ ___ on different types of target cells

different effects

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Acetylcholine effect in heart pacemaker cells

decreases the rate of action potential firing

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Acetylcholine effects in salivary gland cells

stimulates the production of salive

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Acetylcholine effets in skeletal muscle

causes the cells to contract

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Cell surface receptors act as __ __

signal transducers

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Three major classes of cell-surface receptor proteins

Ion-channel-coupled receptors
G-protein coupled receptors
Enzyme-coupled receptors

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- rapid synaptic signaling between nerve cells and other electrically excitable cells - transmitter-gated ion channels or ionotrophic receptors - electrically excitable cells

- Ion-channel-coupled receptors

- act by indirectly regulating the activity of a separate plasma-membrane-bound target protein (enzyme or ion channel)

- G-protein coupled receptors

mediates the interaction between the activated receptor and this target protein

heterotrimeric GTP-binding protein

function as enzymes or associated directly with enzymes

- Enzyme-coupled receptors

covalently adds one or more phosphate groups to specific amino acids on the signaling protein

Protein kinase

removes the phosphate groups

protein phosphate

Two Types of interacellular signaling proteins that act as molecular switches

- Signaling by Phosphorylation - Signaling by GTP binding

Signaling by phosphorylation

- A protein kinase covalently adds phosphate from ATP to signaling protein - A protein phosphate removes the phosphate

Signaling by GTP binding

- GTP binding protein was induced to echcnage GDP to GTP - Activates the protein - The protein then inactivates itself by hydrolizing GTP to GDP

When GTP is bound it is an ___

on state

When GDP is bound it is an

off state

removes the phosphate group

Phosphatases

- drive the proteins into an “off” state by increasing the rate of hydrolysis of bound GTP (off; hydrolysis of GTP)

GTPase-activating proteins (GAPS)

activate GTP-binding proteins by promoting the release of bound GDP on; release bound GDP

Guanin nucleotide exchange factors (GEFs)

bring together groups of interacting signaling proteins into signaling complexes, often before a signal has been received

Scaffold proteins

Types of intracellular signaling complexes

A. REFORMED SIGNALING COMPLEX ON A SCAFFOLD PROTEIN B. ASSEMBLY OF SIGNALING COMPLEX ON AN ACTIVATED RECEPTOR C. ASSEMBLY OF SIGNALING COMPLEX ON PHOSPHOINOSITIDE DOCKING SITES

Give the basic signaling properties that vary in different system

1. Response 2. Sensitivity 3. Dynamic range 4. persistence 5. Signal processing 6. integration 7. coordination

timing varies dramatically in different signaling systems

Response

is often controlled by changes in the number or affinity of the receptors on the target cell - number or affinity; amplification

Sensitivity

tend to act at very low concentrations on their distant target cells - High sensitivity to low concentration of signal

Hormones

operate at much higher concentrations at a synapse, reducing the need for high sensitivity in postsynaptic receptors

Neurotransmitters

A particularly important mechanism for increasing sensitivity

signal amplification

- the responsiveness. closely related to sensitivity - some systems are responsive over narrow range of extracellular signals - some are highly responsive over a much broader range of signal

Dynamic range

response can be transient or prolonged/permanent response

Persistence

allows a response to be governed by multiple inputs.

Integration

Types of abrupt responses

- Sigmoidal response - Discontinous or all-or-none response

smoothly graded response

Hyperbolic

response rises steeply and continuously at intermediate stimulus levels - concentration rises beyond some threshold value

Sigmoidal

the response switches on completely (and often irreversibly) when the signal reaches some threshold concentration

Discontinous or all-or-none response

the output of a process acts back to regulate that same process

Feedback loops

output stimulates its own production

positive feedback

output inhibits its own production

Negative feedback

prolonged exposure to a stimulus decreases the cell’s response to that level of stimulus

Adaptation or desensitization

* largest family of cell-surface receptors * a single polypeptide chain that threads back and forth across the lipid bilayer seven times, forming a cylindrical structure * G-proteins to relay the signal

G-protein-coupled receptors (GPCRs)

What senses does GPCRs operate?

- Sight - Smell - Taste

Three protein subunits that G proteins are composed of

α, β, and γ

is synthesized from ATP by an enzyme called adenylyl cyclase

Cyclic AMP

breaks down cyclic AMP

cyclic AMP phosphodiesterases

stimulatory G protein activates adenylyl cyclase

stimulatory G protein inhibits adenylyl cyclase

ADP ribosylation that alters the Gs α subunit- inactive

cholera toxin

ADP ribosylation of the α subunit of Gi

petussis toxin

phosphorylates specific serines or threonines, regulating their activity

cyclic-AMP dependent protein kinase

cAMP activates the gene that encodes this hormone

somatostatin

CRE-binding (CREB) protein

transcription regulator

stimulates the transcription of the target genes can transform a short cAMP signal into long-term change in a cell

CREB-binding protein (CBP)

G-proteins that activate the plasma-membrane bound enzyme

phospholipase C-β (PLCβ)

is a water-soluble molecule that leaves the plasma membrane and diffuses through the cytosol to the endoplasmic reticulum

IP3

* increases concentration of Ca2+ in the cytosol

IP3-gated Ca2+-release channels (IP3 receptors) Binding of IP3 and Ca2+ into the IP3 receptors

activates a monomeric GTPase (Rho family) which regulates the actin cytoskeleton

G protein called G12

noncolor vision in dim light

rod photoreceptors (rods)

color vision in bright light

cone photoreceptors (cones)

stack of discs; contains cyclic-GMP-gated cation channels

Phototransduction apparatus

decreases the cyclic GMP conc. and closes the cation channel

Light - hyperpolarization

hydrophobic, small, readily pass across the plasma membrane

Nitric Oxide (NO)

Stimulates NO synthesis

Acetylcholine

GPCRs 3 modes of adaptation

1. receptor sequestration 2. receptor down-regulation 3. receptor inactivation

they become altered so that they can no longer interact with G proteins

Receptor inactivation

they are temporarily moved to the interior of the cell so that they no longer have access to their ligand

Receptor sequestration

they are destroyed in lysosomes after internalization

Receptor destruction

Where does desensitization of the GPCRs depends on?

Their Phosphorylation by PKA, PKC or a member of the family of GPCR kinases