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MCM Final > Receptors And Cell Signaling > Flashcards

Receptors And Cell Signaling Flashcards

1
Q

The Leptin gene is _____________ and is the “satiety signal”

Its counterpart ___________ also acts on the hypothalamus and is named the “hunger hormone”

A

Recessive

Ghrelin

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2
Q

___________ alter the activity of different components downstream a signaling event and generate secondary messengers

A

Effectors

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3
Q

____________ signals are transported via blood (hormones) and are ______-lasting.

The ligand can be ______________ or stored in a vesicle

A

Endocrine
Long
Hydrophobic

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4
Q

____________ signals diffuse to neighboring target cells of a different type. These are short lived, local signal molecules

A

Paracrine

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5
Q

What is the main biologic example of paracrine signaling?

A

Neurotransmission

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6
Q

___________ signals occur when secreting cells express surface receptors for that signal

A

Autocrine

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7
Q

Growth factors in cancer cells utilize what type of signaling?

A

Autocrine

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8
Q

Epinephrine released by the adrenal medulla acts on heart muscle - this is an example of what type of signaling?

A

Endocrine

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9
Q

____________ refers to when signal binds to the signaling cell which then binds to receptor on the target cell. This occurs with immune cells.

A

Direct/Juxtacrine

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10
Q

_________ signals freely diffuse accross PM’s

____________ signals undergo gradient-dependent diffusion

___________ signals require an active transport mechanism

_______ signals utilize ion channels

A

Hydrophobic

Small, uncharged, polar

Large, uncharged, polar

Ions

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11
Q

__________ signals are lipid-soluble and diffuse freely through membranes and interact with receptors in the cytosol or nucleus

A

Lipophilic

[note that these must be bound to carrier proteins to be transported through the blood]

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12
Q

What are the 2 different types of lipophilic receptors?

A

Cytoplasmic - form complex with HSP and dissociate upon signal binding, translocating it to the nucleus where it binds a DNA sequence and alters rate of transcription

Nuclear - present in the nucleus bound to DNA. Alters transcription of certain genes after signal binding

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13
Q

Describe hydrophilic signals

A

Water-soluble, cannot diffuse through membrane

Bind to surface receptors and trigger downstream events

Generally small and derived from AA’s, have shorter half lives

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14
Q

What are 2 types of hydrophilic receptors?

A

GPCRs - mediated by G proteins, effector proteins, second messengers, 7-alpha helices

RTKs - mediated by monomeric G proteins and protein kinases, 1-alpha helix

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15
Q

What type of receptor is considered to be in the enzyme-coupled receptor class?

A

RTKs

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16
Q

Epinephrine stimulates glycogen metabolism by promoting __________ secretion

If glycogen stores are depleted, ________ stimulates gluconeogenesis by inducing enzymatic transcription

Under fed conditions, ________ promotes glycogenesis and glycolysis, and inhibits synthesis of gluconeogenesis enzymes

A

Glucagon

Cortisol

Insulin

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17
Q

Oral contraceptives have long half-lives and are taken daily. What type of signal molecules do they contain?

A

Lipophilic

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18
Q

Epinephrine has a short half-life and is administered at the time it is needed. What type of signal does it contain?

A

Hydrophilic

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19
Q

Graves disease is an autoimmune disorder in which thyroid stimulating immunoglobulin binds to and overstimulates TSH receptors, causing hyperthyroidism, including:

Decreased _________

Increased ______ and _______

A

TSH

T3 and T4

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20
Q

What are the clinical manifestations and treatment options for Grave’s disease?

A

CM - weight loss, tachycardia, insomnia, pretibial myxedema, exophtalmos, goiter

TX - surgical resection of thyroid, radioactive iodine

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21
Q

Describe the structural motif of GPCRs

A

ECD binds to signal

TMD composed of 7 alpha helices

ICD interacts with G proteins

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22
Q

GPCRs are arranged in a _______ pattern within the membrane, contain an extracellular ________ bond

They contain conserved _______ and ______ residues as well as a C-terminus tethered to the membrane

A

Circular; disulfide

DRY; WP

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23
Q

GPCRs are active in adrenergic pathways and are targets of ______________, especialle NE and Epi

A

Catecholamines

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24
Q

GPCRs are canonical in structure but diverse in function. What types of ligands can they recognize?

A

Light (rhodopsin), hormones, peptides, proteins, NT’s

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25
Q

The same signaling molecule may produce different physiological responses in the same targets of different cells:

Binding of epi to beta-adrenergic receptors causes _______ of bronchial and intestinal smooth muscle

Binding of epi to beta-adrenergic receptors causes _______ in heart muscle

A

Relaxation
Contraction

[binding produces same second messenger - cAMP - in both, but downstream pathways diverge resulting in diff responses]

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26
Q

Trimeric G proteins have 3 subunits: ______, _____, and ______

They also have ________activity

A

Alpha, beta, gamma

GTPase

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27
Q

trimeric G proteins act as molecular on-off switch

They are on when the ______ subunit is bound to GTP

They are inactive when bound to _______

A

Alpha

GDP

28
Q

_______ are proteins that activate G proteins by promoting exchange of GDP for GTP

A

GEFs (guanine exchange factors)

29
Q

______ proteins speed up the inactivation of G proteins by promoting GTPase activity

A

GAP

30
Q

With GPCRs, once the GTP-bound, alpha-subunit interacts with an effector protein to either activate or inactivate it, it can catalyze reactions that produce second messengers.

What is the typical effector protein in most GPCR-related biologic processes?

A

Adenylyl cyclase

31
Q

True or false: GTP-bound means that the G protein is inactivated because the GTP must be hydrolyzed in order to provide the energy needed for that process

A

False, GTP-bound means that the G protein is activated

32
Q

Which subunit of a trimeric G protein interacts with the effector molecule?

A

Alpha

33
Q

Adenylyl cyclase generates _______ from ATP, which activates _____, which directly regulates many pathways via phosphorylation

A

cAMP

PKA

34
Q

What are 4 methods of PKA regulation?

A
  1. Phosphate group can form part of structure that other proteins recognize
  2. Activation/inactivation of enzymatic target protein
  3. Alteration of IC localization of target proteins
  4. Alterations in abundance of target proteins
35
Q

When a signal molecule binds a GPCR, activating internal G protein Gi, what is the next step?

A

Inhibition of AC

36
Q

Gt activation by light _______ cGMP phosphodiesterase, which is an important process for ____________

A

Activates

Vision

37
Q

_______ cleaves PIP2 into DAG and IP3.

______ then translocates to the ER and opens ligand-gated Ca channels

Increased calcium concentration causes translocation of _____ to plasma membrane where it is activated by DAG so it can phosphorylate _______/_______ of target proteins

Calcium also binds to __________, which activates other downstream targets

A

PLC

IP3

PKC; Ser/Thr

Calmodulin

[moral of the story: Gq activation by PLC activates PKC through secondary process]

38
Q

Certain enzymes hydrolyze cyclic nucleotides to regulate cellular levels. What enzyme hydrolyzes cAMP to AMP?

A

cAMP phosphodiesterase

39
Q

Certain enzymes hydrolyze cyclic nucleotides to regulate cellular levels. What enzyme hydrolyzes cGMP to 5’GMP?

A

cGMP phosphodiesterase

40
Q

Inhibitors of cGMP PDE increase concentration of cellular cGMP, leading to what physiological effect?

A

Smooth muscle relaxation and vasodilation (viagra, levitra, cialis)

41
Q

What effect does caffeine have on cAMP PDE?

A

Inhibits it, thus increasing heart rate

42
Q

Nitric oxide is produced in epithelial cells and is responsible for relaxation of smooth muscles. It diffuses into neighboring muscle and activates _______ ________, leading to the production of cGMP.

What is the desired physiological effect of taking nitrates and what is a possible drug interaction?

A

Guanylate cyclase

Taken to lower blood pressure. These patients should not take drugs that inhibit cGMP PDE (like viagra) which could lead to extreme vasodilation and drops in BP

43
Q

What effect do beta agonists like albuterol and epinephrine have on conditions like asthma?

A

They are beta agonists. Albuterol is hydrophilic and binds to/activates beta-adrenergic receptors

They relax bronchial smooth muscle and stimulate heart muscle contraction

44
Q

What effect do antihistimines have on GPCRs?

A

Inhibitory

45
Q

Histamines, the allergy causing signal molecules derived from _________, bind to the 4 ________ residues in GPCRs

A

Histidine; histidine

46
Q

Cholera is usually contracted due to the consumption of water contaminated with the cholera toxin. This causes ribosylation of ________ residues and ________ GTPase activity.

A

Arg; decreases

So Gsa remains active and overstimulated AC produces too much cAMP –> intestinal cells open Cl channels –> loss of electrolytes and water –> diarrhea

47
Q

What effect does the pertussis toxin have on G proteins?

A

ADP ribosylation of Cys on Gia prevents activation and dissociation of a-subunit from G protein complex

So less inhibition of AC, and overproduction of cAMP leads to fluid loss and excess mucous in airway epithelial cells

48
Q

___________ refers to the ability to turn off or “ignore” a signal

A

Desensitization

49
Q

What are 4 possible mechanisms for signal desensitization?

A
  1. Hormone levels drop (decreased AC activity, decreased cAMP, decreased PKA activity)
  2. Removal of signal molecule (PDE removes cAMP/cGMP)
  3. Receptor sequestration
  4. Receptor destruction
50
Q

GRKs ____________ GPCRs, then ___________ binds to the 3rd intracellular loop, preventing Ga from interacting with third loop. The result is that Ga-GDP does not get converted to Ga-GTP

A

Phosphorylate

Arrestin

51
Q

Enzyme-coupled reactions occur via RTKs. First, a signal binds to the ECD and induces a conformational change that causes dimerization of the receptor. Specific tyrosine residue is phosphorylized (autophosphorylation). What is the next step?

A

Phosphotyrosine is recognized and bound by adapter and docking proteins (SH2 domain of Grb2), leading to downstream signaling pathways that are RAS dependent or independent

52
Q

What would be the result of a mutation or other allosteric effecter causing dimerization of an RTK?

A

The RTK will remain active

53
Q

________ domains are found on adaptor proteins that recognize and bind to motifs on the receptors that contain phosphorylated Tyr

A

Recognition

Examples: SH2 or PTB

54
Q

What is the difference between activated Ras and inactivated Ras?

A

Ras-GTP = active

Ras-GDP = inactive

[regulated by MAPkinase pathway]

55
Q

What would happen if Ras were inhibited by an intracellular injection of Ras-inactivating antibodies?

A

Cell may no longer respond to some of the EC signals

56
Q

What would happen if Ras were permanently switched on?

A

Cell would begin proliferating uncontrollably –> cancer

57
Q

Given its ability to cause uncontrolled cell division if mutated, what type of gene is Ras?

A

Proto-oncogene

58
Q

Insulin signaling occurs via RTK with intermediate scaffold including _______, which binds either Grb2 (Ras dependent) or ________ (Ras independent)

A

IRS-1

PI3 kinase

59
Q

What is the result of the Ras-dependent insulin signaling pathway?

A

Grb-2 = Ras dependent scaffold

Alters gene transcription –> increased transcription of glucokinase

60
Q

What is the result of the Ras-independent insulin signaling pathway?

A

PI3 kinase = Ras independent scaffold

Alters protein and enzyme activity –> increased GLUT4 movement to plasma membrane; activation of glycogen synthase

61
Q

What specific mutation occurs with Ras to turn it from a proto-oncogene to an oncogene?

A

Mutation decreases GTPase activity and locks Ras in the active, GTP-bound state

62
Q

Neurofibromatosis is related to Ras, but Ras is not the issue with this type of cancer. What is the mutation?

A

NF-1 gene, which encodes a GAP for Ras, so RAS is uncontrollably activated in pathways for nerve tissue growth

63
Q

_______ are the target of pharmacologic inhibitors in certain types of cancer. The breast cancer drug herceptin targets HER2, which belongs to this receptor family.

A

RTKs

64
Q

Insulin resistance leads to type II diabetes. One critical aspect is a loss of insulin stimulation of glucose uptake by GLUT4 transporters in adipose and skeletal tissue.

Studies point to reduced activation of ____ by insulin in obese subjects. A source of impairment is probably IRS 1 and 2.

A

PKB

65
Q

What is one of the most direct routes for affecting transcription in terms of signaling?

A

JAK-STAT receptors - transmit info from EC chemical signals to the nucleus resulting in DNA transcription and gene expression

These act as cytokine receptors

MCM Final (14 decks)

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