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Cell Biology > Exam 4 (Hyder-Signaling) > Flashcards

Exam 4 (Hyder-Signaling) Flashcards

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1
Q

What are the 2 types of receptors

A

cell-surface receptors
intracellular receptors

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2
Q

Which receptor type are most receptors part of?

A

cell-surface receptors

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3
Q

Explain Intracellular receptors

A

cell talks to itself
ligand binds to receptor –>
intracellular proteins = response

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4
Q

What are the 3 steps in a signaling pathway?

A
  1. Reception
  2. Transduction
  3. Response
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5
Q

What are the 3 types of cell response?

A

altered metabolism
altered gene expression
altered cell shape / motility

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6
Q

What are the 2 functions of intracellular signaling?

A
  1. “switches” to turn on/off pathways in cell
  2. Amplify signal
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7
Q

What are the two types of intracellular signaling? which is more common?

A

Kinases (most common)
G-proteins

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8
Q

What do kinases do?

A

phosphorylate amino acids on proteins

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9
Q

What are two types of kinases?

A

serine/threonine kinase
tyrosine kinase

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10
Q

G-proteins

A

intrinsic GTPase to turn on/off pathways
bind GTP

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11
Q

In G-proteins, if GTP is bound pathway is (on/off) and if GTP is hydrolyzed the pathway is (on/off)

A

GTP bound = on
GTP hydrolyzed = off

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12
Q

Two types of G-proteins

A

small monomeric G-proteins
large, trimeric GTP-binding proteins

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13
Q

What is an example of a small monomeric G-protein?

A

Ras

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14
Q

What is an example of a large, trimeric, GTP-binding protein?

A

G-Protein Coupled Receptors (GPCR)

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15
Q

What are the 4 types of external cell signaling?

A
  1. Contact-dependent
  2. Paracrine/Autocrine
  3. Synaptic
  4. Endocrine
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16
Q

Contact Dependent (external) cell signaling

A

ligand binds to cell surface
target cell MUST contact signal cell

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17
Q

Paracrine / Autocrine (external) cell signaling

A

cell secretes molecule that signals to same cell or different cell

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18
Q

Paracrine cell signaling

A

secretes molecules that act on different cell

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19
Q

Autocrine cell signaling

A

secretes molecules that act on same cell

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20
Q

Synaptic (external) cell signaling

A

axons allow long-range signaling
Type of paracrine signaling

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21
Q

Endocrine (external) cell signaling

A

molecules secreted into blood for long-range signaling
cells need receptor to respond

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22
Q

What is an example of endocrine cell signaling?

A

estrogen (hormone) released & picked up by cells with estrogen receptor

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23
Q

What are the 3 types of cell-surface receptors?

A

Ion-channel coupled receptors
G-protein coupled receptors (GPCR)
Enzyme-coupled receptors

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24
Q

Ion-channel coupled receptors

A

ionotropic / ligand-gated
ion channel opens when ligand binds

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25
Q

What is an example of an ion-channel coupled receptor?

A

Acetylcholine release at NMJ

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26
Q

What is the function of G-protein coupled receptors?

A

receptors carry signal to effector protein in the cell

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27
Q

GTP –> GDP = (activation/inactivation) of G proteins

A

inactivation

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28
Q

What are the 3 subunits of G-proteins

A

Beta
Gamma
Alpha

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29
Q

Which G-protein subunit binds GTP?

A

Alpha

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30
Q

What are the 4 parts of the alpha subunit in G-proteins

A

Gs
Gi
Gq
G12/13

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31
Q

What does Gs do?

A

activate adenylyl cyclase to make cAMP
(opens calcium channels)

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32
Q

What do Gi do?

A

inhibits adenylyl cyclase

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33
Q

What does Gq do?

A

activates PLC to make IP3 & DAG

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34
Q

What does G12/13 do?

A

activates Rho (monomeric G-protein)
regulates actin cytoskeleton

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35
Q

What does GAP do?

A

activates GTPase
up GTP –> GDP
= “off switch”

36
Q

What does GEF do?

A

releases GDP –> GTP
activates “on switch”

37
Q

Mechanism for GPCR Activation

A
  1. ligand binds = GPCR active
  2. GDP released from G-protein
  3. G-protein = activated and subunits separate
  4. Subunits activate/inactivate targets
  5. GTP hydrolyzed –> GDP
  6. G-protein subunits reassemble
38
Q

What are 2 ways GPCR is inactivated?

A
  1. GPCR kinase (GRK) + arrestin
  2. Signal Adaptation
39
Q

What is the mechanism for GPCR kinase + arrestin (inactivation of GPCR)

A
  1. ligand binds to GPCR = active
  2. GPCR stimulates GRK to phosphorylate GPCR
  3. Arrestin binds to GPCR
40
Q

What are the two modes of enzyme-coupled receptors?

A
  1. internal kinase activity
  2. associated kinase activity
41
Q

Internal Kinase Activity (enzyme-coupled receptors)

A

own enzymatic activity
ligand binds 2 receptors –> activate kinase via phosphorylation

42
Q

What are 3 important growth factors?

A

EGF
PDGF
VEGF

43
Q

What are two types of internal kinase activity?

A

Receptor Tyrosine Kinases
Receptor Serine/Threonine Kinases

44
Q

What are 3 receptor tyrosine kinases?

A

InsR
EGFR
VEGFR

45
Q

What is a type of receptor serine/threonine kinase?

A

TGFB receptor

46
Q

Mechanism for TGFB receptor

A

Smad protein is phosphorylated
Smad4 forms complex and goes to nucleus for protein synthesis = wound healing

47
Q

What diseased state has a high TGFB receptor (high smad)

A

Lobular Dissecting Hepatitis

48
Q

What type of receptors are present in associated kinase activity?

A

cytokine receptors (interleukins, interferons, TNFa)

49
Q

What pathway is associated with the Interleukin & Interferon receptors?

A

JAK-STAT pathway

50
Q

Explain mechanism for JAK-STAT pathway

A

JAK is phosphorylated = active
leads to phosphorylation/activation of STAT

51
Q

What drug inhibits JAK (which inhibits JAK-STAT)?

A

Apoquel

52
Q

What pathway is associated with the inflammatory TNFa family receptors?

A

NFkB pathway

53
Q

What turns on the NFkB pathway?

A

P50 / P65

54
Q

Mechanism for NFkB pathway

A

P50/P65 enter nucleus and release mRNA for inflammatory proteins

55
Q

What do P50/P65 act as?

A

transcription factor

56
Q

What diseased state is associated with the NFkB pathway?

A

Canine Large B-cell Lymphoma
(Excessive NFkB activation)

57
Q

What are two examples of drug therapy on signaling pathways?

A

chlorpromazine
meclizine

58
Q

Prostaglandins (PGE2)

A

mediators in pain/inflammation
pro & anti-inflammatory response depending on receptor subtype that binds

59
Q

What diseases are associated with EP1 on Gq?

A

colorectal cancer | neurological disease

60
Q

What diseases are associated with EP2 on Gs?

A

glaucoma | ocular hypertension | bone formation

61
Q

What disease is associated with EP3 on Gi?

A

cardiovascular disease

62
Q

What diseases are associated with EP4 on Gs (with B-arrestin)?

A

ulcerative colitis | solid tumors | bone formation | B-cell lymphoma | cardiovascular disease

63
Q

What are the two causes of cancer?

A

imbalance of growth
apoptosis

64
Q

Proto-oncogenes

A

genes that produce normal products and stimulate normal cell development
common in growth/survival signaling

65
Q

Fos & Jun (proto-oncogenes) function

A

proliferation of cells

66
Q

What proto-oncogenes activate Fos & Jun?

A

Src
Ras
Raf

67
Q

Oncogenes

A

develop mutations of proto-oncogenes
stimulate unregulated cell division/growth

68
Q

Viral Oncogenes

A

viruses change normal cells to cancer cells

69
Q

Mechanism for Viral Oncogenes

A

virus brings in oncogene with mutation
can integrate viral genome into host

70
Q

What is an example of a viral oncogene in cats?

A

FeLV –> lymphosarcoma

71
Q

What are 4 ways proto-oncogenes can turn to oncogenes?

A
  1. deletion/point mutation
  2. regulatory mutation
  3. gene amplification
  4. chromosome rearrangement
72
Q

Example of proto-oncogene –> oncogene by point mutation

A

Ras

Raf phosphorylates Mek –> phosphorylates Erk = change protein activity or gene expression

73
Q

Example of proto-oncogene –> oncogene by translocation

A

BCR –> BCR-ABL
connection to JAK-STAT pathway

74
Q

What drug can bind/block substrate from binding to BCR-ABL?

A

Gleevec (imatinib)

75
Q

Gleevec (imatinib)

A

competitive inhibitor for tyrosine kinase
kills tumor cells

76
Q

What diseases are treated by Gleevec?

A

Chronic Myeloid Leukemia (CML)
Gastrointestinal Stromal Tumors (GIST)

77
Q

What are two things that if effected, can cause cancer?

A

tumor suppressor genes
oncogenes

78
Q

What do Receptor Tyrosine Kinase (RTK) activate that are beneficial to cancer?

A

angiogenesis
cell proliferation

79
Q

What activates Receptor Tyrosine Kinases in normal cell?

A

ligand binds –> dimerization
undergo conformational change
relay signal downstream

80
Q

What mediates in RTK signaling?

A

Ras GTPase

81
Q

What are 4 ways for pharmacological treatment of cancer?

A
  1. target Ras
  2. oncolytic therapy
  3. drug to suppress angiogenesis
  4. target RTK
82
Q

Drugs which target RTK antibodies for cancer treatment end in (nib/mab)

A

Mab

83
Q

Drugs which use small molecule inhibitors for cancer treatment end in (nib/mab)

A

Nib

84
Q

What growth factor is secreted for tumor angiogenesis?

A

VEGF

85
Q

Oncolytic therapy

A

Normal cell doesn’t have active Ras, but cancer cell does
Virus kills tumor cell, NOT normal ones and immune system responds

86
Q

Drugs ending in “mab” use ____ for cancer treatment

A

Antibodies

Cell Biology (6 decks)

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