lecture 22 : cell signalling Flashcards by Jillian Kucey

what is autocrine signalling

acts on the same cell that releases the ligand

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whats endocrine signalling

long signalling usually through bloodstream

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whats paracrine signalling

acts on neighbouring cells

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what is a second messenger

molecule produced intracellularly in response to activation of receptor

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what do effector proteins produce

target cell responses

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what is signal amplification

one response creates a cascade of them - such as many second messenger molecules

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whats the first messenger

binding of a single ligand to a receptor

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what does a second messenger do

enables cells to mount a large scale response (amplification)

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whats positive feedback regulation

product acting on earlier molecule to increase activity

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whats negative feedback regulation

product acting on earlier molecule to inhibit activity

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what are some examples of fast cell signalling

cell movement
secretion
metabolism

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what are some examples of slow cell signalling

cell differentiation
cell growth and division

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what do kinases do

adds phosphate groups

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what do phosphatases do

remove phosphate groups

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what receives the message to alter cell a activity

target proteins

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signalling pathways consist of a series of __________

proteins

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what are the 2 main types of proteins kinases

serine/threonine kinases
tyrosine kinases

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what causes the different responses to the same molecule in cells

the receptor

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whats receptor sequestration

removing receptor from surface (time out in endosome)

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whats receptor down-regulation

degradation of receptor through a lysosome

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what regulates cell behaviour

various combination of signal molecules

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what are the 3 types of receptors

ion channel coupled receptors
G protein coupled receptors
enzyme coupled receptors

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whats the drug target receptor

G protein coupled receptors

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whats the structure of a G protein coupled receptors

7 a-helical transmembrane domains

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what ligands bind to G protein coupled receptors

natural ligands

what does a G protein coupled receptor do to a pathway

either activation or inhibition

whats the structure of G proteins

heterotrimeric

what are the 3 subunits of heterotrimic G proteins

a subunit B subunit y subunit

what 2 subunits are lipid tethered in G proteins

a subunit y subunit

what does an inactive G protein look like

alpha subunit is bound to GDP

whats an active G protein

alpha subunit with GTP disassociated from the other subunits

what phosphorylates the G protein coupled receptor

G protein-coupled receptor kinase

what does the phosphorylated G protein coupled receptor bind to? why?

arrestin to prevent the receptor from activating G proteins

what are the 2 things needed to terminate a G protein coupled receptors response

1. phosphorylate receptor by G protein coupled receptor kinase (GRK) 2. binding of arrestin

what often happens to arrestin bound receptors

endocytosis

what happens to receptors trapped in clathrin coated pits

bud into the cytoplasm

resensitized:

returning vesicle/its contents back to plasma membrane

what are the hydrophobic second messengers (1)

DAG

what are the hydrophilic second messengers

cAMP IP3 Ca2+

what are the 4 signal transductions by GPCRs

Gs Gi Gq G12/13

what does Gs do

stimulates cAMP pathways

what does Gi do

inhibits cAMP pathway

what does Gq do

activates the inositol phosphate pathway

what does G12/13 do

not really sure (forget about it)

whats the common main target for the cAMP pathway and G proteins

adenylyl cyclase

what are the two second messengers derived from phosphatidylinositol 4,5 bisphophate

inositol triphosphate (IP3) Diacylglycerol (DAG)

what converts PIP2 to inositol triphosphate (IP3) and Diacylglycerol (DAG)

phospholipase C

what does DAG do?

activates protein kinase C (PKC)

what is activated by cAMP in cAMP signalling

protein kinase A

what is the second messenger in Gs

cAMP

what is the second messenger in Gi

cAMP

what is the second messgenger for Gq

DAG + IP3

whats the structure of an enzyme coupled receptor

single transmembrane a helix

how do enzyme coupled receptor translate the extracellular signal

dimerization

what are the 2 mechanisms for receptor dimerization

ligand mediated dimerization receptor mediated dimerization

what is ligand mediated dimerization? whats an example of a ligand that does this ?

ligand brings the receptors together (example is PDGF)

what is receptor mediated dimerization? whats an example of a receptor?

a ligand that causes a conformational change to bring receipts together (EGF is an example)

what kind of activity can enzyme coupled receptors have

they can have intrinsic enzyme activity or be associated with an enzyme

what does dimerization activate

kinase domains

where do receptors phosphorylate each other

tyrosine residues

what is RAS a member of

monomeric GTPase

what subunit does RAS most resemble

alpha subunit

what is an RTK

receptor tyrosine kinases

when GTP is bound to RAS, what is it

Active

when GDP is bound to RAS, what is it

inactive

what does RAS require to exchange GDP to GTP

activating protein RAS GEF

what limits the duration of RAS signalling

RAS-GTPase-activating proteins (GAPS)

what signals the phosphorylation of sequence of serine/threonine kinases after activating RAS protein

MAP kinase signalling module pathway

what part of RAS phosphorylates the effectors

activated MAP kinase

what kind of pathway is the MAP kinase signalling module

serine/threonine kinase based

what is the PI-3-kinase-Akt signalling pathway

pathway related to cell growth/survival

what signalling molecule uses PI-3-kinase-Akt signalling pathway

insulin like growth factors (IGFs)

what phosphorylates inositol phospholipids in plasma membrane

phosphoinositide 3-kinase (PI-3-kinase)

what happens to phosphorylated inositol phospholipids

they become docking sites for cytosolic intracellular signalling proteins

what docks to phosphorylated inositol phospholipids

protein kinase 1 Akt

what is Atk also called

protein kinase B (PKB)

what kind of kinase is Atk

serine/threonine kinase

what does activated Atk do

inactivates proteins that it phosphorylated

what phosphorylates Bad

Atk (protein kinase B)

what does a non phosphorylated bad mean?

apoptosis will be induced because bad is actively bound to Bcl2

what does Bcl2 on its own do

inhibit apoptosis