Lecture 16- Cell Signaling II

Question 1

three main classes of cell surface receptors

Answer 1

• ion channel coupled receptors
• G-protein coupled receptors
• enzyme coupled receptors

Question 2

ion channel coupled receptors

Answer 2

• causes change of permeability of plasma membrane to specific ions, thus change of membrane potential
• very rapid responses (within milliseconds)
• especially impt in nerve and muscle cells

Question 3

application of changing electric potential

Answer 3

changing electric potential of egg membrane quickly blocks polyspermy in sea urchins

Question 4

G-protein coupled receptors (GPCRs)

Answer 4

• most numerous class of receptors (>700 in humans)
• most studied
• mediate diverse biological responses (smell, sight)
• can be activated by wide variety of signaling molecules
• frequent target of drugs

Question 5

all GPCRs have similar structure

Answer 5

seven-pass transmembrane proteins

Question 6

GPCRs activate G proteins

Answer 6

• these G proteins have 3 subunits (trimeric), different from monomeric small G proteins
• tethered to plasma membrane
• signal binding causes conformational change in receptor that is transmitted to its cytoplasmic domain
• activated receptor acts as GEF for its G protein
• activated Gα and Gβγ can each activate different effector proteins
• once activated, a GPCR can activate many molecules of G protein

Question 7

subunits of G proteins (trimeric)

Answer 7

• α
• β
• γ

Question 8

many G proteins activate membrane-bound enzymes that produce small messenger molecules

Question 9

two major targets of GPCRs

Answer 9

• phospholipase C (PLC)

- adenylyl cyclase (generates cAMP)

Question 10

phospholipase C leads to production of two small messenger molecules

Answer 10

phospholipase C cleaves inositol phospholipid to produce -> inositol 1,4,5-triphosphate (IP3) and diacylglycerol (DAG)

Question 11

IP3 can lead to release of Ca2+ from ER

Answer 11

increases cytosolic Ca2+ level, which acts as a second messenger to trigger many biological processes

Question 12

fertilization of an egg by sperm triggers an increase in cytosolic calcium levels in the egg (activates PLC), causing

Answer 12

• physical changes of the egg shell to prevent more than one sperm from entering the egg
• activation of the egg so that embryonic development in initiated

Question 13

DAG, in combination with Ca2+, can activate protein kinase C (PKC)

Answer 13

this activation leads to new protein synthesis during fertilization

Question 14

cell responses mediated by phospholipase C activation

Answer 14

• vasopressin targets liver, causes glycogen breakdown
• acetylcholine targets pancreas, causes secretion of amylase (digestive enzyme)
• acetylcholine targets smooth muscle, causes contraction
• thrombin targets blood platelets, causes aggregation

Question 15

G-protein α subunit switches itself off

Answer 15

• normally α subunit hydrolyzes its bound GTP to GDP within seconds
• can also be aided by ‘GAP-like’ proteins in the cell

Question 16

process of α switching off

Answer 16

• hydrolysis of GTP by α subunit inactivates this subunit and causes it to dissociate from target protein
• inactive α subunit reassembles with βγ complex to reform an inactive G protein
• target protein is inactive, inactive G protein

Question 17

G protein-coupled receptors

Answer 17

• seven pass transmembrane proteins
• function by activating trimeric G proteins (α,β,γ) subunits
• G proteins cycle between GTP bound and GDP bound states
• many G proteins activate enzymes that produce second messengers
• two main target enzymes of G proteins: phospholipase C (producing IP3 -> Ca2+ and DAG, together -> PKC) and adenylyl cyclase (producing cAMP -> PKA)

Question 18

enzyme coupled receptors

Answer 18

receptors can act as or associate with enzymes

Question 19

receptor tyrosine kinases (RTKs)

Answer 19

• represents one of the largest class of enzyme coupled receptors
• activated by growth factors (signals), such as FGF (fibroblast growth factor), EGF (epidermal growth factor)
• their cytoplasmic domains function as tyrosine protein kinases
• they regulate growth, proliferation, differentiation, and survival of cells

Question 20

most RTKs activate small GTPase Ras

Answer 20

(see slide 24 of notes)

Question 21

Ras stimulates cell proliferation via MAP kinase pathway

Answer 21

• pathway is MAPKKK -> MAPKK -> MAPK (mitogen activated protein kinase), thus cell proliferation
• MAPK stimulates changes in protein activity and changes in gene expression
• some other cancer mutations affect proteins that function in the same pathway as Ras

Question 22

a signal transduction pathway involves multiple components

Answer 22

primary transduction -> relay -> transduce and amplify -> integrate/feedback -> distribute -> altered metabolism/cell shape or movement/gene expression

Question 23

signaling pathways can be highly interconnected

Answer 23

(see slide)