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Exam 4 (Hyder-Signaling) Flashcards

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
What is an example of an ion-channel coupled receptor?
Acetylcholine release at NMJ
26
What is the function of G-protein coupled receptors?
receptors carry signal to effector protein in the cell
27
GTP --> GDP = (activation/inactivation) of G proteins
inactivation
28
What are the 3 subunits of G-proteins
Beta Gamma Alpha
29
Which G-protein subunit binds GTP?
Alpha
30
What are the 4 parts of the alpha subunit in G-proteins
Gs Gi Gq G12/13
31
What does Gs do?
activate adenylyl cyclase to make cAMP (opens calcium channels)
32
What do Gi do?
inhibits adenylyl cyclase
33
What does Gq do?
activates PLC to make IP3 & DAG
34
What does G12/13 do?
activates Rho (monomeric G-protein) regulates actin cytoskeleton
35
What does GAP do?
activates GTPase up GTP --> GDP = "off switch"
36
What does GEF do?
releases GDP --> GTP activates "on switch"
37
Mechanism for GPCR Activation
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
What are 2 ways GPCR is inactivated?
1. GPCR kinase (GRK) + arrestin 2. Signal Adaptation
39
What is the mechanism for GPCR kinase + arrestin (inactivation of GPCR)
1. ligand binds to GPCR = active 2. GPCR stimulates GRK to phosphorylate GPCR 3. Arrestin binds to GPCR
40
What are the two modes of enzyme-coupled receptors?
1. internal kinase activity 2. associated kinase activity
41
Internal Kinase Activity (enzyme-coupled receptors)
own enzymatic activity ligand binds 2 receptors --> activate kinase via phosphorylation
42
What are 3 important growth factors?
EGF PDGF VEGF
43
What are two types of internal kinase activity?
Receptor Tyrosine Kinases Receptor Serine/Threonine Kinases
44
What are 3 receptor tyrosine kinases?
InsR EGFR VEGFR
45
What is a type of receptor serine/threonine kinase?
TGFB receptor
46
Mechanism for TGFB receptor
Smad protein is phosphorylated Smad4 forms complex and goes to nucleus for protein synthesis = wound healing
47
What diseased state has a high TGFB receptor (high smad)
Lobular Dissecting Hepatitis
48
What type of receptors are present in associated kinase activity?
cytokine receptors (interleukins, interferons, TNFa)
49
What pathway is associated with the Interleukin & Interferon receptors?
JAK-STAT pathway
50
Explain mechanism for JAK-STAT pathway
JAK is phosphorylated = active leads to phosphorylation/activation of STAT
51
What drug inhibits JAK (which inhibits JAK-STAT)?
Apoquel
52
What pathway is associated with the inflammatory TNFa family receptors?
NFkB pathway
53
What turns on the NFkB pathway?
P50 / P65
54
Mechanism for NFkB pathway
P50/P65 enter nucleus and release mRNA for inflammatory proteins
55
What do P50/P65 act as?
transcription factor
56
What diseased state is associated with the NFkB pathway?
Canine Large B-cell Lymphoma (Excessive NFkB activation)
57
What are two examples of drug therapy on signaling pathways?
chlorpromazine meclizine
58
Prostaglandins (PGE2)
mediators in pain/inflammation pro & anti-inflammatory response depending on receptor subtype that binds
59
What diseases are associated with EP1 on Gq?
colorectal cancer | neurological disease
60
What diseases are associated with EP2 on Gs?
glaucoma | ocular hypertension | bone formation
61
What disease is associated with EP3 on Gi?
cardiovascular disease
62
What diseases are associated with EP4 on Gs (with B-arrestin)?
ulcerative colitis | solid tumors | bone formation | B-cell lymphoma | cardiovascular disease
63
What are the two causes of cancer?
imbalance of growth apoptosis
64
Proto-oncogenes
genes that produce normal products and stimulate normal cell development common in growth/survival signaling
65
Fos & Jun (proto-oncogenes) function
proliferation of cells
66
What proto-oncogenes activate Fos & Jun?
Src Ras Raf
67
Oncogenes
develop mutations of proto-oncogenes stimulate unregulated cell division/growth
68
Viral Oncogenes
viruses change normal cells to cancer cells
69
Mechanism for Viral Oncogenes
virus brings in oncogene with mutation can integrate viral genome into host
70
What is an example of a viral oncogene in cats?
FeLV --> lymphosarcoma
71
What are 4 ways proto-oncogenes can turn to oncogenes?
1. deletion/point mutation 2. regulatory mutation 3. gene amplification 4. chromosome rearrangement
72
Example of proto-oncogene --> oncogene by point mutation
Ras Raf phosphorylates Mek --> phosphorylates Erk = change protein activity or gene expression
73
Example of proto-oncogene --> oncogene by translocation
BCR --> BCR-ABL connection to JAK-STAT pathway
74
What drug can bind/block substrate from binding to BCR-ABL?
Gleevec (imatinib)
75
Gleevec (imatinib)
competitive inhibitor for tyrosine kinase kills tumor cells
76
What diseases are treated by Gleevec?
Chronic Myeloid Leukemia (CML) Gastrointestinal Stromal Tumors (GIST)
77
What are two things that if effected, can cause cancer?
tumor suppressor genes oncogenes
78
What do Receptor Tyrosine Kinase (RTK) activate that are beneficial to cancer?
angiogenesis cell proliferation
79
What activates Receptor Tyrosine Kinases in normal cell?
ligand binds --> dimerization undergo conformational change relay signal downstream
80
What mediates in RTK signaling?
Ras GTPase
81
What are 4 ways for pharmacological treatment of cancer?
1. target Ras 2. oncolytic therapy 3. drug to suppress angiogenesis 4. target RTK
82
Drugs which target RTK antibodies for cancer treatment end in (nib/mab)
Mab
83
Drugs which use small molecule inhibitors for cancer treatment end in (nib/mab)
Nib
84
What growth factor is secreted for tumor angiogenesis?
VEGF
85
Oncolytic therapy
Normal cell doesn't have active Ras, but cancer cell does Virus kills tumor cell, NOT normal ones and immune system responds
86
Drugs ending in "mab" use ____ for cancer treatment
Antibodies

Cell Biology (6 decks)

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