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Pharm Block 1 > Signal Transduction > Flashcards

Signal Transduction Flashcards

1
Q

Steps involved in signal transduction

A

Traverse the plasma memebrane
Transduced through cytoplasm to nucleus
Change gene expression

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2
Q

Definition of Paracrine Signaling

A

Local mediators secreted by signaling cell to surrounding target cells

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3
Q

Definition of Autocrine Signaling

A

Mediators are secreted and received by same cell

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4
Q

Definition of Synaptic Signaling

A

NT release from neuron to a post-synaptic target (neuron or myocyte)

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5
Q

Definition of Endocrine Signaling

A

Hormone release into blood stream to carry them to distant target

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6
Q

Definition of plasma membrane-bound receptor

A

Signaling molecule is a TM protein whose extracellular domain is a ligand for receptor on target cell
Direct contact between cells

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7
Q

Definition of Intracellular Steroid Signaling

A

Lipophilic signaling molecules that interact in cytoplasm or nucleus, receptors are ligand-activated TFs

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8
Q

Components of steroid receptor

A

Hormone-binding site
DNA-bindgin domain
Transcription-activating domain

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9
Q

Action of steroid receptor upon binding to steroid

A

Dissociation from inhibitory proteins so DNA-domains can bind

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10
Q

Glucocorticoid Receptor Mechanism

A

Cortisol carried by corticosteroid-binding globulin (CBG)
Cortisol activates glucocorticoid receptor (GR) in cytoplasm
GR dissociates from IP and HSP70 to enter nucleus and activate effector site (GRE)

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11
Q

Therapeutic importance of glucocotricoids

A

Agents for anti-inflammatory regulation

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12
Q

Types of membrane receptors

A

Ion Channel-Linked - Ligand regulates channel permeability
GPCR - Nuff said
Enzyme-Linked Receptor - Ligand activates enzymatic activity on receptor’s catalytic domain

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13
Q

5-Subunit Ionotropic Receptors

A

ACh, GABA, Serotonin, Glycine

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14
Q

4-Subunit Ionotropic Receptors

A

Glutamate

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15
Q

Structure and Mechanism of Nicotinic AChR

A

5 Subunits - Alpha 1/2, Beta, Gamma, Delta
ACh binds to alpha subunits to open the channel
Cation influx causes depolarization (excitatory)

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16
Q

Location of Nicotinic AChR

A

Neuromuscular Junction (NMJ)
PNS
CNS

17
Q

GABA Mechanism

A

GABA binds to receptor
Cl channel opens
Influx of Cl
Hyperpolarization and inhibitory response

18
Q

Barbituate and benzodiazepine effect on GABA receptors

A

Cause GABA receptors to be hypersensitive to GABA

19
Q

Signalers of GPCRs

A 
Neurotransmitters
Light
Odorants
Hormones
Growth Factors
Cytokines
20
Q

What links GPCR to effector enzymes?

A

Heterotrimeric G proteins

21
Q

Subunits of G proteins

A

G-alpha: Binds to GTP, interacts with effectors, GTPase activity
G-beta/gamma: Inhibits alpha, anchors to membrane, has its own effectors

22
Q

Types of G-alpha subunits

A

Gαs - Stimulates adenylyl cyclase
Gαi - Inhibits andeylyl cyclase
Gαq - Activates PLC

23
Q

Tyrosine Kinase Receptor - Structure

A

Single protein with one TM which dimerizes upon binding of ligand or two subunits which tetramizes upon binding of ligand
Usually have a tyrosine kinase domain in cytosol but can bind with separate tyrosine kinase

24
Q

Effects of ligand binding on Tyrosine Kinase Receptor

A

Dimerization
Cross-autophosphorylation
Binding of intracellular signaling molecules

25
Q

Clinical consideration of Tyrosine Kinase-Linked Receptors

A

Cell proliferation and differentiation
Hormones, such as insulin
Growth Factors: EGF, PDGF, VEGF

26
Q

Example of Serine/threorine-specific protein kinases

A

PKA, PKC
Ca/calmodulin-dependent kinase (CaM Kinase)
MAP Kinases (ERK, JNK, or p38 kinase)

27
Q

Definition of dual specificity kinases

A

Phosphorylates both threonine and tyrosine

Example: Certain MAP Kinases

28
Q

cAMP Generation

A

Gαs - Activates adenylyl cyclase, activated adenylyl cyclase converts ATP to cAMP

29
Q

cAMP Effector

A

PKA

30
Q

DAG/IP3 Generation

A

Gαq activates Phospholipase C to cleave PIP2

31
Q

DAG/IP3 Effector

A

DAG activates PKC

IP3 releases calcium from the ER

32
Q

Calcium generation

A

Generation: Generated by opening of ion channels

33
Q

Calcium effectors

A

Effectors: Binds to proteins and activates PKC and other kinases and enzymes

34
Q

Examples of Monomeric G Proteins

A

Ras, Rho, Rac, Rap, Rab

AKA: Small GTPases, p21 proteins

35
Q

Regulation of monomeric G proteins

A

Activation by GEFs (Guanine Nucleotide Exchange Factors)

Deactivation by GAPs (GTPases Activating Proteins)

36
Q

Ras-MAP Pathway

A

TRK + Adapter + GEF -> Ras (Activated monomeric G protein) -> Raf (MAPKKK) -> MKK1 (MAPKK) -> ERK (MAPK) -> MAP (Transcription Factor)
GEF: SOS
Adapter: GRB2

37
Q

Clinical significance of EGF Receptor

A

Mutations cause cell proliferation
Gefitinib and erlotinib are tyrosine kinase inhibitors, tumor supressors (80% efficacy in mut. EGFR patients/10% efficacy in normal EGFR patients)
EGFR mutations more common in female Asian non-smoker adenocarcinoma patients

38
Q

Definition of attenuation of signal

A

Turning off signaling molecules

39
Q

Accomplishing attenuation of signal

A

Ligand inactivation or dissociation from the receptor
Receptors dissociate
Adaptor protein complexes dissociate
GTPase activity of G proteins
Kinase vs phophatases
Second messengers are metabolized or diffuse away
Ions are sequestered or pumped out

Pharm Block 1 (4 decks)

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