Ch 15 - cell signaling + transduction

PTB

phosphotyrosine binding domain

PH

binds phosphoinositides

SH2

binds phosphotyrosine

SH3

binds proline rich regions

GTPase Activating protein

activates GTP hydrolysis and regulates GTPase activity (1 of 2 major regulators; GAP)

Guanine Nucleotide Exchange Factor

activates the exchange of GDP for GTP, stimulating GTPase activity (1 od 2 major regulators; GEF)

Signal

any molecule, ion, or stimulus that carries information to trigger a response in a cell/organism

Receptor

protein that receives and binds to a specific signal, then starts a response in the cell

Transduction

process of converting a signal into a series of steps inside the cell that leads to a response; passing a message along a chain inside the cell until it reaches the part that does the job

Response

final outcome/cellular change that occurs after a signal is received and transduced

Hydrophilic

water loving

Hydrophobic

water fearing

Cell surface receptor

protein located on the outer plasma membrane of a cell that binds to signaling molecules and initiates a cellular response inside the cell

Intracellular receptor

protein found inside the cell that binds to signaling molecules that can pass through the cell membrane such as small, nonpolar, or lipid soluble molecules

Contact dependent

cells must physically be in contact with each other to communicate

Paracrine

releases a chemical signal; only surrounding cells get the message (must be in same tissue environment)

Autocrine

cell releases signaling molecules that bind to receptors on its own surface; cell talks to itself

Synaptic

specialized cell to cell communication that occurs between neurons and a target cell across a synapse; involves neurons and neurotransmitters

Endocrine

signal can activate cells far away; hormones

Gap junction

direct connection between cells; common in muscle cells

Apoptosis

when no communication occurs, no signals are received or sent; automated cell death

Acetylcholine

a neurotransmitter (chemical messenger) that transmits signals across synapses; can have different responses depending on the cell that receives it

Morphogen gradient

different concentrations of morphogen can determine how a cell responds; forms across developing tissues and provides positional information to cells guiding their fate

Half life

amount of time it takes for half of a substance to be degenerated; different signals can have varying amount of this time frame

Nuclear receptor superfamily

large group of intracellular receptors that function as ligand activated transcription factors; regulate gene expression

Inhibitory protein

protein that prevents/decreases the activity of another protein, enzyme, or signaling pathway by blocking or slowing down a specific cellular process

Transcription activating domain

region of a transcription factor that interacts with other protein to increase the rate of gene transcription

DNA binding domain

region of transcription receptor that binds specifically to DNA sequences allowing the protein to regulate gene expression

Primary response

initial cellular response triggered by the first wave of gene activation after a signaling event; involves the production of immediate early proteins that can regulate further gene expression

Secondary response

the later cellular response that occurs after the primary response; involves genes activated by proteins produced during the primary response; regulate more specialized/long term changes in the cell

Ion channel coupled receptor

cell surface receptor that opens or closes an ion channel in response to binding a signaling molecule (ligand), allowing ions to flow across the membrane

G protein coupled receptor

cell surface receptor; activates an intracellular G protein when a signaling molecule binds; looks like the subunits separating from each other

Enzyme coupled receptor

cell surface receptor that acts like an enzyme itself or associates with enzymes; activated receptors change structure and do something

Scaffold

builds a structural framework; recruits, binds, and organizes proteins

Relay

process of passing a signal from one molecule to another

Transducer

converges a signal from one form to another within a cell; helps to amplify the signal

Amplifier

increases strength of a signal; amplifies the signal

Integrator

brings info together from multiple sources

Bifurcation protein

spread information

Anchor

anchor something to cytoskeleton filaments; locks it in place

Modulator

can increase/decrease activity of a particular protein

Effector proteins

proteins that carry out the final response in a signaling pathway

Molecular switches

light switch/dimmer analogy; can be on/off or have gradual changes like a dimmer light switch

Phosphoinositide

type of phospholipid found in cell membranes that can be phosphorylated to form signaling molecules

Proline rich region

protein sequence containing many proline amino aicds; the SH3 domain likes to bind here

Positive feedback

increases the stimulus

Negative feedback

reduces the stimulus

Receptor desensitization

how to turn signaling pathway off

Receptor sequestration

pull receptor out of the membrane; can be returned

Receptor down regulation

degrades the receptor

Receptor inactivation

protein binding event blocks the message

Signaling protein inactivation

doesn’t block the receptor but something else along the signaling pathway

Production of inhibitory protein

inhibitory protein blocks communication

G protein

molecular switch inside the cell that is activated by a G protein coupled receptor (GPCR) to transmit signals by binding and hydrolyzing GTP

Trimeric GTPase

a G protein made of 3 subunits (alpha and beta gamma)

Alpha subunit

binds GTP/GDP; dissociates upon activation and regulates target proteins

Beta gamma subunit

the paired subunits of a trimeric GTPase that remain together and can regulate signaling proteins when released from the alpha subunit after G protein activation

Adenylyl cyclase

enzyme activated by G proteins that converts ATP into cyclin AMP (cAMP); a key secondary messenger in signaling pathways

Cyclic AMP

secondary messenger made from ATP that activates PKA

cAMP dependent protein kinase (PKA)

serine/threonine kinase activated by cAMP that phosphoylates target proteins

Regulatory subunits

inhibitory components of PKA that bind + block the catalytic subinits when cAMP is absent; when cAMP binds, they release the active catalytic subunits

Catalytic subunits

active components of PKA that are released when cAMP binds to the regulatory subunits which allows them to phosphorylate target proteins

cAMP reponse element binding protein (CREB)

transcription factor activated by PKA phosphorylation that binds to DNA at cAMP response elements that stimulate gene transcription

CREB binding protein (CBP)

coactivator proteins that binds to phosphorylated CREB and helps activate transcription by remodeling chromatin

cAMP response element

specific DNA sequence in gene promoters that CREB binds to in order to regulate gene transcription in response to cAMP signaling

Phospholipase C beta (PLCB)

enzyme activated by GPCR that cleaves a membrane phospholipid into 2 messgeners; IP3 and DAG

Phosphatidylinositol 4,5 biphosphate

membrane phospholipid that is cleaved by phospholipase C (PLC) to produce IP3 and DAG

Diacylglycerol (DAG)

lipid derived second messenger that activates protein kinase C (PKC)

Inositol 1, 4, 5 triphosphate (IP3)

water soluble second messenger that binds to receptors on the ER causing a release of calcium ions into the cytoplasm

Calcium dependent protein kinase (PKC)

activated by DAG and increased intracellular calcium which phosphorylate target proteins to regulate various cellular functions

Frequency

rate at which a signaling event or oscillation occurs; can influence the strength and type of cellular responses

Amplitude

strength/intensity of a signaling event/level; refers to the concentration/magnitude of a signaling molecule

Duration

length of time a signaling event or signal remains active; influences the nature and extent of the cellular response

Location

the specific cellular or subcellular site where a signaling event acts; can determine outcome of the signal

Calmodulin

small calcium binding protein that changes shape when bound to calcium; activates various target proteins

Ca/Calmodulin dependent protein kinase (CaM kinase)

protein kinase activated by the calcium calmodulin complex that phosphorylates target proteins

Inactive

state of protein/signaling molecule when it is not currently active or performing its function

Activated

state of protein or signaling molecules when it is switched “on” and able to perform its function; often triggered by ligand binding, phosphorylation, or conformational change

Fully active

state in which a protein/signaling molecule is maximally activated and capable of performing its full biological function

Calcium independent activity

ability of a protein to remain active even after calcium levels drop; often due to phosphorylation

G protein coupled receptor kinase (GRK)

an enzyme that phosphorylates activates GPCPs, marking them for binding by arrestins

Arrestin

binds to phosphorylated GPCRs; desensitizes the receptor

Receptor tyrosine kinase (RTK)

dimerizes and autophosphorylates on tyrosine residues

Ras GTPase

small monomeric G protein that acts as a molecular switch; active when bound to GTP, initiating the MAP kinase cascade

Protein kinase cascade

series of kinases that sequentially activate one another by phosphorylation

MAP kinases

group of protein kinases activated in a cascade that regulate gene expression, cell growth, and division

location, amplitude, frequency, duration

the 4 features of a calcium signaling event