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Biochemistry 2 > Biosignaling > Flashcards

Biosignaling Flashcards

1
Q

What is signal transduction?

A

Non covalent interaction a ligand and a receptor

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2
Q

4 major features of signal transduction

A

Specificity; Amplification; Desensitization/adaptation; Integration

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3
Q

Features of specificity (4)

A

Complementarity; non-covalent bond (so it can end); tissue-specific receptor/receptor target

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4
Q

Do every cells express receptors?

A

No

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5
Q

Can differentiated cells can have similar receptors?

A

Yes, but may respond differently: it explains why a single hormone can affect many cells

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6
Q

Explain specificity of TRH

A

Thyrotrophin releasing-hormone is secreted from hypothalamus to control expression of thyroid gland and TSH, but it has no effect on hepatocytes (lack of receptor)

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7
Q

Explain specificity of adrenalin

A

Affects glycogen metabolism in hepatocytes, but not adipocytes (receptors in both, but the last ones can’t express a response)

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8
Q

Amplification is responsible for…

A

Enzyme cascade of action (it explains relative speed of action)

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9
Q

What is desensitization/adaptation of signal transduction?

A

No more response to an actual signal.

Eg.: Smell, bright to dark light, skin sensation of clothes

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10
Q

Integration is a feature of signal transduction…

A

Ultimate response depends on what type of signal are coming in (somation)

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11
Q

Some signals to which cells respond…

A

Antigens, glycoproteins, oligosaccharides, xtracellular matrix components, growth factors, hormones, light, mechanical touch, neurotransmitters, nutrients, odorants, pheromones, tastants

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12
Q

A ligand-receptor interaction can have a direct response (inducing a change) or…

A

Further levels of interaction inducing activity of effectors which then respond

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13
Q

There are six major types of receptors…

A

G-protein coupled; tyrosine kinase; guanylyl cyclase; ashesion (integrin); gated ion channel; nuclear

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14
Q

What is the special class of receptor?

A

Nuclear ones (in the nucleus)

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15
Q

G protein-coupled in short

A

External ligand binds to receptor; it activates an intracellular GTP-binding protein, which regulates an enzyme that generates a second messenger (the actual response)

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16
Q

Example of G-protein receptor?

A

Epinephrine

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17
Q

First step of G prot

A

1- Substrate-receptor interaction (non-covalent)

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18
Q

2nd step G prot

A

2- GDP-Gs become GTP-Gs activated (phosphorylated by GTP)

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19
Q

3rd step G prot

A

3- GTP-Gs activated moves to adenylyl cyclase and activates it

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20
Q

4th step G prot

A

Adenylyl cyclase catalyzes the formation of cyclic AMP

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21
Q

5th step of G prot

A

cAMP activates PKA (protein kinase A)

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22
Q

6th step of G prot

A

PKA phosphorylates other proteins, producing a response

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23
Q

7th step of G prot

A

cAMP is degraded, no longer activation of PKA

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24
Q

What is the enzyme activated in the G prot example of epinephrine?

A

Adenylyl cyclase

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25
Q

What is the second messenger regulated by the enzyme in G prot example of epinephrine?

A

cAMP

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26
Q

How does the second messenger induces a response to epinephrine?

A

cAMP activates PKA, which phosphorylates concerned cell components

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27
Q

What is the actual G prot?

A

GDP-Gs + y and B subunits. It desactivates itself with intrinsic GTPase activity (when activated)

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28
Q

When is the GDP-Gs prot is bound to B and y subunits?

A

When inactivated

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29
Q

What is the precursor of second messenger?

A

ATP

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30
Q

What is the enzyme activating the second messenger?

A

Adenylyl cyclase

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31
Q

Anatomy of PKA

A

Core: AKAP, 2x C (catalytic) and R (regulatory) subunits

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32
Q

What is the conformation of PKA when inactive; when active?

A 
Inactive = C bound to R
Activated = C (also substrate-binding cleft) free and R are facing the opposite
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33
Q

What is activating PKA?

A

4 cAMP that bind to R subunits, switching their conformation

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34
Q

cAMP is acting on which specific aa (3)?

A

Serine and threonine, + tyrosine

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35
Q

3 enzymes regulated by cAMP-PKA?

A

Glycogen synthase; phosphorylase kinase b; pyruvate kinase

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36
Q

Other G-coupled receptors example?

A

Ghrelin; gonadopropin; thyrotropin hormone; prostaglandins

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37
Q

How does signal amplication work, and to which fold?

A

Enzyme cascade; 10 000 folds

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38
Q

There are two possible ends for G-coupled signals

A

cAMP cut into AMP; intrinsic GTPase activity (GAP, GTPase activator protein, and RGS, regulator of g-protein signaling)

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39
Q

What are the role of GTP-GDP exchange factors?

A

To stimulate activation of GTP-Gs activated by GTP

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40
Q

What are the GTP-GDP exchange factors?

A

rh: rhodopsin; Sos: Son of Seven

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41
Q

Signal desensitization in G-prot: step 1

A

Epinephrine binds to its receptor and activates GTP-Gs activated

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42
Q

Signal desensitization in G-prot: step 2

A

GsBy (subunit left behind) recrutes bARK (b-adrenergic receptor kinase) to the membrane, which phosphorylates the receptor

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43
Q

How does bARK phosphorylates the receptor?

A

Ser residues of its carboxyl end

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44
Q

How many phosphorous groups added from bARK?

A

2

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45
Q

Signal desensitization in G-prot: step 3

A

B-Arrestin (B-Arr) binds to the phosphate groups (carboxyl terminal of the receptor)

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46
Q

Signal desensitization in G-prot: step 4

A

B-Arr-receptor enters the cell by endocytosis

47
Q

Signal desensitization in G-prot: step 5

A

In endocytosis vesicle, B-Arr dissociates and receptor is dephosphorylated + returned to the membrane

48
Q

When does epinephrine stop from being bind to the receptor during desensitization?

A

Step 3-4: when B-Arr binds to the carboxyl end of the receptor

49
Q

What is localization/nucleation?

A

Phenomenon from which AKAP5 binds to several enzymes so that G-Prot signal transduction is localized, not diluted and limited

50
Q

Signaling through IP3 and Ca2+: what does that mean?

A

Other type of GPCR: instead of adenyl cyclase and cAMP, it is phospolipase C, PIP2, IP3 and Ca2+

51
Q

What are the second messengers in IP3 signaling?

A

PIP2 (a phospholipid), IP3 and Ca2+

52
Q

What are the steps of signaling through IP3 and Ca2+?

A

Starts as epinephrine; Gq activated binds to PIP2 specific-PLC; it activates the production of 2 messengers: IP3 and diacylglycerol; IP3 travels to ER where it binds to IP3-gated Ca2+ channels, releasing sequestred Ca2+; diacylglycerol+Ca2 activate PKC, which phosphorylates others..

53
Q

PIP2 is…

A

A phospholipid bound to PLC

54
Q

IP3 and diacylglycerol are obtained from…

A

The breakdown of PIP2 when Gq activated reaches PLC

55
Q

Diacylglycerol is what and found where..?

A

Phospholipid with half-head; in the membrane

56
Q

IP3 is what and found where?

A

Half-head of a phospholipid, soluble; travels from the membrane to the ER membrane when PLC is activated

57
Q

Some signals acting through IP3

A

Acetylcholine; Histamine; Oxytocin; Serotonin

58
Q

Tyrosine kinase receptor in short

A

Lingand-binding extracellular face, a transmembrane segment and an enzyme active site which is a protein kinase that phosphorylates Tyr residues on a Tyr kinase

59
Q

Examples of Tyr kinase receptor?

A

Insulin and growth factors

60
Q

Describe active insulin receptor protein (INSR)

A

Two a subunits at the xtracellular face + two B subunits at the intracellular face

61
Q

Where is the Tyr phosphorylated, and where does the phosphate come from?

A

Hydroxyl group of Tyr residues; phosphorylated by ATP

62
Q

How many Tyr residues does the whole Tyr kinase receptor phosphorylate?

A

6 (3 x 2 B subunits)

63
Q

Where are the Tyr residues to be phosphorylated?

A

Near the carboxyl end of B subunits (they form the B subunits)

64
Q

Why do we call B subunits phosphorylation of Tyr residues AUTOphosphorylation?

A

It is not a phosphorous group coming from an extern component

65
Q

What does autophosphorylation induce?

A

It opens up the active site, so the enzyme would phosphorylate other Tyr residues on other targeted proteins

66
Q

Step 1 of MAP kinase pathway

A

Autophosphorylation

67
Q

MAPK step 2

A

Insulin receptor substrate-1 (IRS-1, a targeted protein) is phosphorylated on many of its Tyr residues

68
Q

MAPK step 3

A

IRS-1 becomes a nucleation for: one of its phosphorylated Tyr binds to SH2 domain of Grb2 which relies IRS-1 to Sos by SH3; Sos catalyzes GDP-GTP exchange on Ras (a G-prot), which becomes activated

69
Q

MAPK step 4

A

Activated Ras binds Raf-1, which becomes activated

70
Q

MAPK step 5

A

Activated Raf-1 phosphorylates MEK on two of its Ser residues; which activates it so it can phosphorylate ERK on a Thy and a Tyr residues, activating it.

71
Q

MAPK step 6

A

Phosphorylated ERK moves into nucleus and phosphorylates nuclear transcription factors, as Elk1

72
Q

MAPK step 7

A

Phosphorylated Elk1 joins SRF to activate the transcription of targeted genes

73
Q

What is MAPK regulating?

A

Gene expression

74
Q

What is PIP3 signaling?

A

In Tyr kinase family as MAPK, but instead of Grb2, IRS-1 binds to another cascade of enzymes

75
Q

What does it have for response?

A

Glycogen synthesis

76
Q

PIP3 signaling step 1

A

IRS-1 binds to SH2 domain of PI3K; PI3K converts PIP2 to PIP3 (phosphorylation)

77
Q

PIP3 signaling step 2

A

PKB is binding to phosphorylated PIP3 and is phosphorylated by PDK1 to be activated. Once activated, it phosphorylates GSK3 on a Ser residue, inactivating it

78
Q

What is the role of GSK3?

A

Convert glycogen synthase to its inactive form

79
Q

PIP3 signaling step 3:

When GSK3 is inactivated by PKB, by being phosphorylated on its Ser residue…

A

It can’t convert glycogen synthase to its inactive form, so glycogen synthase remains active

80
Q

PIP3 signaling step 4

A

Synthesis of glycogen is accelerated

81
Q

PIP3 signaling step 5

A

PKB stimulates glu transporter GLUT4 to travel from cytosol vesicles to plasma membrane, thus accelerating glucose intake

82
Q

What is the JAK-STAT pathway?

A

It has no intrinsic Tyr kinase, but when its external receptor is bound, it can bind a cytosolic Tyr kinase

83
Q

Example of JAK-STAT pathway?

A

Regulation of erythrocytes formation

84
Q

JAK-STAT pathway step 1

A

When the lingant binds, receptor dimerizes thus binds and activates JAK, which phosphorylates the receptor on its Tyr residues

85
Q

JAK-STAT pathway step 2

A

Phosphorylated Tyr residues of receptor can bind STAT5 and thus positioning it so it can be phosphorylated by JAK

86
Q

JAK-STAT pathway step 3

A

Phosphorylated STAT5 dimerizes, causing it to be transported into the nucleus, to stimulate gene expression of erythrocytes formation

87
Q

JAK-STAT can also act in a different pathway

A

It can trigger the MAPK pathway

88
Q

What is cross-talk among signaling system?

A

Signaling pathways are interconnected; they can increase or decrease the power of the others

89
Q

Receptor guanylyl cyclase can be described as…

A

There are two types of receptors

90
Q

What is the first type of guanylyl cyclase receptor?

A

Homodimer with a single membrane-spanning segment in each momomere; it detects two xtracellular ligands: AN factor, from renal collecting ducts and vascular smooth muscles + guanylin, from the intestine (to secrete Cl-)

91
Q

What is the catalytic pathway for guanylyl cyclase receptor 1?

A

From GTP to cGMP

92
Q

What is the second type of guanylyl receptor?

A

Soluble heme-containing enzyme which is activated by nitric oxide (NO); heart muscles and blood vessels

93
Q

What is the role of guanylyl cyclase receptor?

A

Regulating blood volume and pressure through Na excretion

94
Q

Both pathways of guanylyl cyclase stimulate which protein kinase?

A

PKG

95
Q

What is the enzyme that activates cGMP from GTP?

A

Guanylyl cyclase

96
Q

What is the enzyme that inactivates cGMP

A

cGMP PDE (cGMP phosphodiesterase)

97
Q

What is the resting potential of a normal animal cell membrane?

A

-50 to -70 mV

98
Q

What are the high concentration ions inside the cell?

A

Cl- and K+

99
Q

What are the high concentration ions outside the cell?

A

Na+ and Ca2+

100
Q

What is the normal distribution of Na+K+ATPase?

A

3 Na+ out, 2 K+ in (which explains the negative potential inside)

101
Q

Ion channels are specific as they only allow…

A

Cations OR anions to enter/quit the cell

102
Q

Gated ion channels are crucial to…

A

Hormone secretion, sensory processes, nerve conduction, learning and memory

103
Q

Which ions depolarize the membrane?

A

Cl-, Na+, Ca2+

104
Q

Which ion hyperpolarize the membrane?

A

K+

105
Q

Stimulus pathway

A

A stimulus opens a Na channel, which depolarizes the membrane, stimulating the opening of other Na+ channels; K+ channels open right after the repolarize the membrane, waiting for the next action potential; when the membrane potential reaches the axon terminal, Ca2+ gated channels open, allowing Ca2+ to entry; internal concentration of Ca2+ triggers the exocytosis of neurotransmitters in the synaptic cleft; the neurotransmitters bind to their specific post synaptic neuron as the Na+ and Ca2+ ions enter the post synaptic neuron (continuation of the action potential)

106
Q

Anatomy of a Na+ gated channel

A

Funnel-opening on the extracellular side, an ion selectivity filter, a central aqueous activity and the activation domain on the cytoplasmic side

107
Q

Acetylcholine receptor description

A

The M2 helice is the only one that can allow Na+, Ca2+ or K+ to cross; it is opened only when acetylcholine binds to it (2); acetylcholine induces a switching conformation that hides the five big Leu residues (hydrophobic), and are replaced by small polar residues

108
Q

Integrins: adhesion receptors

A

They regulate adhesion of cells to each other

109
Q

Integrins pathway in 4 steps

A

Collagen binds to integrin, sending an outside-in signal; cytoplasmic side response induces change in cytoskeleton and gene expression; talin triggers in cytoskeleton inside-out signal; outside response with cell adhesion or migration or assembly of extracellular matrix

110
Q

How many different types of integrins?

A

24

111
Q

How do integrins work?

A

By recognition sequences

112
Q

Signal transduction in integrins is…

A

Bidirectional

113
Q

Integrins mediate…

A

Immune response: blood clothing, angiogenesis, tumor metastasis

114
Q

Nuclear receptors in four steps

A

1- Hormone-serum prot travels from the plasma membrane to its specific receptor in the nucleus
2- The hormone induces a changing conformation of its receptor (inducing change in the other receptors as well), which binds to its specific regulatory region (HRE) in DNA
3- Binding regulates transcription of genes
4- The altered level of hormone-induced gene provoke a response in cell activity

Biochemistry 2 (3 decks)

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