Lecture 15: Cell communication-signalling through G-protein coupled receptors Flashcards Preview

BIOC 341 > Lecture 15: Cell communication-signalling through G-protein coupled receptors > Flashcards

Flashcards in Lecture 15: Cell communication-signalling through G-protein coupled receptors Deck (87):
1

Why is intercellular communication necessary? 

• Cellular differentiation and specialization 

• Growth stimulation or termination 

• Tissue formation 

• Integration of metabolism 

2

General Signaling Pathway?

A image thumb
3

What are the three types of effector proteins?

  • metabolic enzyme
  • transcription regulatory protein
  • cytoskeletal protein

4

4 types of signal distribution?

  • contact-dependent
  • paracrine/autocrine
  • synaptic
  • endocrine

A image thumb
5

What is the fast effect of signaling?

  • altered protein function

6

What is the slow effect of signaling?

  • altered protein synthesis

7

Endocrine signals are ___ in concentration and its receptors are ____ affinity

low conc

high affinity

8

Synaptic signals are ___ in concentration and its receptors are ____ affinity

high conc

low affinity

9

Chemical types of signaling molecules

• Amino acid derivatives 

• Nucleotides 

• Lipids 

– Steroids 

– Arachidonic acid metabolites

-eicosanoids 

– Retinoids 

• Peptides 

• Gases 

– Nitric Oxide (NO) 

– Carbon Monoxide (CO) 

• Protons 

– C. elegans muscle 

10

Amino Acid derived signals are ____

shorter lifespan, more paracrine-like

11

Steroid signals are relatively ____ lasting

long

12

Steroid signals are derived from ____'s structure

cholesterol

13

Eicosanoids are derived from ___'s structure

arachodonic acid

14

Peptide hormones include:

  • Pituitary hormones
  • hypothalamic hormones
  • thyroid hormones
  • digestive hormones
  • pancreatic hormones

15

Nitric Oxide is a ____

vasodilator

16

Nitric oxide synthase transforms ____ into NO and citroline

arginine

17

NO diffuses out of the ____ cell into the ____ cell

endothelial to smooth muscle

18

What is the name of the cytosolic intracellular receptor NO binds to?

guanyl cyclase

19

Membrane soluble signals (those that bind to intracellular receptors) require ____ to navigate the aqeous environment outside the cells

carrier proteins

20

Cell-surface receptors usually bind to ____ signals.

hydrophilic

21

Intracellular receptors

• Nuclear receptor superfamily 

• Steroid hormone receptors are ligand-activated transcription factors 

• They are modular in construction 

– Ligand binding domain 

– DNA-binding domain 

– Variable region 

• Generally function with other binding partners 

22

What are the three domains of a steriod receptor? where are they located?

N-terminus: transcription-activating domain

Middle: DNA-binding domain

C-terminus: ligand-binding domain

23

Response induced by steroid hormone receptor activation 

A image thumb
24

The presence of a hormone or ligand is sensed by an ____

integral membrane protein receptor

• This information is communicated across the cell membrane and transmitted by intracellular signaling molecules. 

25

Small intracellular mediators are also referred to as ____

“second messengers” 

26

Second messengers illicit various cellular responses: 

-Activate or inhibit specific protein targets 

-Increase or decrease gene transcription 

27

3 types of cell surface receptors?

• Ion channels coupled receptors 

• G-protein coupled receptors 

• Enzyme-linked receptors 

28

A nicotinic acetylcholine receptor is___

an ionictropic receptor

29

A muscarinic acetylcholine receptor is ____

a metabotropic receptor

30

Enzyme-linked receptors____

dimerize to form catalytic domains

31

Common Second Messangers:

  • cAMP
  • cGMP
  • DAG (diacylglycerol)
  • IP3 (inositol triphosphate)

32

cAMP

activates protein kinase A (PKA)

33

cGMP

Activates protein kinase G (PKG) and opens cation channels in rod cells

34

DAG

activates protein kinase c (PKC)

35

IP3

Opens ca2+ cannels in the ER

36

What are the two forms of molecular switches in singaling?

-signaling by phosphorylation

-signaling by GTP binding

37

A intracelllular signaling protein is ON when it's ____ or bound to____. It's OFF when it's ____ or ____

ON- phosphorylated or bound to GTP

OFF- dephosphorylated or bound to GDP

38

protein kinases ___ a phosphate from ___

remove a phosphate from ATP and add it to the intracellular signaling protein

39

protein phosphatases ____ the intracellular signaling protein

dephosporylate (remove a phosphate)

40

GEF proteins-

-help GTP to bind by ejecting GDP

41

GAP

cuts of the terminal phosphate of GTP (Deposphorylates it to GDP)

42

Tyrosine Kinase receptors

-add phosphate from ATP to tyrosine residues

43

Which amino acid side chains get phosphorylated?

Tyrosine (Y), Serine (S), Threonine (T)

44

Signal integration

Multiple signals and their receptors can affect the same intracellular signaling molecule

45

What are the three types of intracellular signaling complexes?

  • preformed signaling complex on a scaffold protein
  • assembly of signaling complex on activated receptor
  • assembly of signaling complex on phosphoinositide docking sites

46

What signaling pathway involves all three types of intracellular signaling complexes?

The insulin signaling complex

47

Receptor sequestration

A image thumb
48

Receptor down-regulation

A image thumb
49

receptor inactivation

A image thumb
50

Inactivation of signaling protein

A image thumb
51

Production of inhibitory protein

A image thumb
52

General G-protein activation

A image thumb
53

G-protein coupled receptors (GPCRs)

• Seven transmembrane domains 

• Responds to very diverse ligands 

– Photons 

– Peptide hormones 

– Eicosanoids 

– Amino acid derivatives 

• Largest family of cell surface receptors in eukaryotes 

– >1,000 devoted to smell alone in mice 

• About half of all known drugs work through Gprotein coupled receptors

54

For GPCRs the C-terminus is on the ____ side and the N-terminus is on the ____ side.

C=cytosolic side

N=extracellular side

55

The βγ subunit...

function as a unit and has never been shown to be separate in the cell. 

56

The α-subunit is....

postranslationally modified by the addition of myristic acid to the N-terminus. 

57

The γ-subunit is....

postranslationally modified by the addition of a polyisoprenoid, usually farnesyl. 

58

These hydrophobic modifications (to the  βγ subunit)...

serve to localize the complex to the membrane, its site of action.

59

the α-subunit has...

A ras domain and an AH (alpha-helical) domain

60

On a G-protein, the gdp binding spot is on the ___ subunit

alpha

61

 β-adrenergic receptor is a...

G-protein coupled receptor

62

G-protein effectors: 

• Ion channels 

• Adenylyl cyclase 

• Phospholipase Cβ 

• cGMP Phosphodiesterase

63

Adenylyl cyclase produces _____

cAMP

64

The ___ subunit of G-protein interacts with adenylate cyclase

65

Adenylate kinase has ___ catalytic domains.

66

How does cAMP produce a cellular response?

It binds to a protein kinase (PKA)

67

Activated PKA bind to ____ to produce___

inactive CREB, CREB -binding protein (CBP)

68

CBP binds to ___

cyclic AMP response element (CRE) which activates a target gene for transcription

69

Acute response of cAMP

-phosphorylation of protein involves in glycogen metabolism 

70

Delayed response of cAMP

- increase in synthesis of the somatostatin gene 

71

Ser/Thr protein phosphatases ____ the action or protein kinases

reverse

72

Four types of protein phosphatases

 -Type I (dephosphorylates most PKA substrates) 

– Type IIA (broad specificity, main PPTase) 

– Type IIB (aka Calcineurin, regulated by Ca2+) 

– Type IIC (minor player) 

73

G-protein activation of PLCβ

• Phospholipase C beta 

• PLCβ is activated by specific Gα-subtypes 

• Gqα, Goα, and Goβγ activate PLC 

74

Phosphatidylinositides

-phospolipase release IP3 from glycerol back bone, forming IP3 and diacylglycerol

-diacylglycerol (DAG) activates PKC

-IP3 releases ca2+ from the ER

A image thumb
75

76

Calcium is sometimes used as a ____

second messenger

77

Positive and negative feedback produce ____

 calcium waves

A image thumb
78

Ca2+ homeostasis is maintained by...

  • Membrane pumps:
    • Na+ driven Ca2+ exchanger
    • Ca2+ Pump

79

What three mechanism help to maintain low cytosolic Ca2+ levels?

  • Ca2+ pump in ER membrane
  • Ca2+ binding molecules in the cytoplasm
  • active Ca2+ import into the mitochondria

80

Ca2+ signaling effects are mediated by which three Ca2+ binding proteins?

  • Troponin C
  • Synaptotagmin
  • Calmodulin

81

Troponin C 

– Muscle contraction 

82

Synaptotagmin 

– Neurotransmission 

83

Calmodulin 

– Multipurpose Ca2+ receptor involved in many responses 

– Binds 4 Ca2+ ions, need two or more or adopt an active conformation 

84

How does Calmodulin change conformation upon Ca2+ binding?

Its two domains wrap around its target protein

85

What are the three types of Ca2+-Calmodulin-dependent protein kinases?

  • Narrow Substrate specificity
    • Myosin light chain kinase  (smooth muscle contraction)
    • Phosphorylase kinase (glycogen breakdown)
  • Broad substrate specificity
    • CaM-Kinase II 

86

What does activated CaM kinase II do? 

• Its mechanism of activation allows past calcium influxes to be “remembered” 

• The enzyme also changes its activity in response to calcium oscillations 

– It can react to frequency and amplitude of calcium spikes 

• Important for learning an memory in the brain 

87

_____ can sense Ca2+ oscillations 

CaM kinase II