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Biochemistry > Second Messenger Signaling, Insulin Signaling, Steroid Signaling > Flashcards

Second Messenger Signaling, Insulin Signaling, Steroid Signaling Flashcards

1
Q

Target cells bind to ____ via ___ embedded w/in plasma membrane or w/in cytoplasm

A

. Signaling molecules

. Protein receptors

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2
Q

Categories cell signaling receptors

A

. G-linked protein receptors: amplification of signals via intracellular signaling molecules (second messengers)
. Catalytic via phosphorylating Tyr residues in intracellular substances
. Intracellular receptors allow cells to respond to hydrophobic signaling molecules

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3
Q

G-protein linked receptors structure

A

. Heterotrimeric G-proteins (alpha, beta, and gamma subunits)
. Transmembrane
. 7 membrane-spanning regions
. Contain extracellular ligand-binding domains and intracellular domains that initiate signaling rxns

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4
Q

T/F there around close to 400 G-protein coupled receptors identified in humans

A

T

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5
Q

G protein general signaling mechanism

A

. After ligand binding transmembrane receptor protein confirmation changes and binds to/activates G-protein
. activated on cytoplasmic surface of plasma membrane
. Bind to GTP when activated
. Have GTPase activity that aids in eventual deactivation
. Individual subunits dissociate after GTP binding

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6
Q

Type of G protein activate depends on ___

A

Signaling molecule and type of target cell

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7
Q

Alpha subunit in G protein

A

. Interacts w/ and regulates function of intracellular enzyme localized to plasma membrane

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8
Q

Second messengers

A

. Products of enzymatic rxns
. Relay signal from ligand into cell
. Amplify original signal
. Regulate activity of Ser/Thr kinases that then phosphorylate substrates

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9
Q

End result of signaling cascade

A

. Biological response by the cell

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10
Q

Enzymes acted on by G proteins

A

. Adenylyl cyclase

. Phospholipase C

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11
Q

Second messenger regulated by adenylyl cyclase

A

cAMP

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12
Q

cAMP regulates ____

A

Protein kinase A (PKA)

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13
Q

Cholera

A

. Toxin that modifies alpha-subunit of Gs in intestinal epithelial cells
. Inhibits the alpha-polypeptide from cleaving GTP to GDP causing overproduction of cAMP in intestinal cells
. Causes continuous transport of Na and water into the lumen of the gut
. Causes diarrhea and dehydration assoc. w/ cholera

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14
Q

Pertussis

A

. Toxin disrupts normal activity of Gi inhibiting its alpha subunit
. Adenylate cyclase is not turned off when it should be

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15
Q

G proteins that regulate phospholipase C

A

Gq alpha (Same basic mechanism activates G protein and phospholipase C as in GSalpha signaling)

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16
Q

Catalytic receptors signal via phosphorylation of ____

A

Tyr residues

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17
Q

Receptors w/ intrinsic Tyr kinase activity

A

. 3 domains: ligand-binding portion w/ NH2 terminus, alpha helical domain that spans lipid bilayer, and effector region in intracellular portion of the protein
. Single transmembrane receptor chain forms dimers upon ligand binding

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18
Q

Mechanism of signaling in TKRs

A

. Catalytic receptor w/ Tyr kinase activity switches on enzyme activity of its intracellular domain when signaling molecule binds to its extracellular domain
. Binding of signaling molecule causes 2 receptor molecules to come together in membrane forming dimer
. Contact btw 2 adjacent intracellular receptor tails activates Tyr kinase function
. Each receptor tail Tyr phosphorylates the other

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19
Q

Adaptor proteins

A

. Intracellular signaling proteins that bind to phosphorylate Tyr residues
. Bind in cytoplasmic domain of receptors
. Share SH-2 and SH-3 domains

20
Q

Ras

A

GTP-binding protein
. Molecular switch for key signaling in control of growth and differentiation
. Small G protein
. Homologous w/ alpha subunit of heterotrimeric G proteins

21
Q

Percentage of tumors that have constitutively active forms of Ras causing abnormal growth

A

30%

22
Q

T/F Ras contains SH2 domain

A

F. Binds to Sh-2 containing adaptor proteins that bind to Tyr phosphorylated receptors

23
Q

MAP kinase cascade

A

Ser/Thr phosphorylation cascade activated by Ras

24
Q

Final enzyme in MAP kinase cascade

A

Mitogen activated protein kinase (MAPK)
. Gets phosphorylated, translocated to nucleus, and phosphorylated transcription factors that induce transcription of gene

25
Q

STATs

A

. Signal transducers and activators of transcription
. SH-2 containing latent cytoplasmic proteins that can bind to Tyr-phosphorylated residues w/in cytoplasmic domains of receptors w/ own catalytic activity
. Sometimes involved in signaling by non-receptor Tyr kinases

26
Q

When bound/docked w/ phosphorylated Tyr residues, STATs are acted on by _____

A

Receptor Tyr kinase and become Tyr phosphorylated

27
Q

What occurs w/ Tyr-phosphorylated STATs

A

Formed imers and then translocations to nucleus
. Bind to DNA
. Activate transcription of responsive genes

28
Q

Signaling via non-receptor Tyr kinases

A

. Don’t possess own Tyr kinase activity but activate non-receptor Tyr kinase
. Cytoplasmic domain of receptors non-covalently assoc. w/ cytoplasmic Tyr kinase proteins
. phosphorylate Tyr residues w/in receptor tail

29
Q

Best characterized non-receptor Tyr kinases

A

. Src family tyrosine kinases

. Janus Kinases

30
Q

Insulin signal via catalytic receptors w/ ____

A

Intrinsic Tyr kinase activity

31
Q

What happens after insulin binds to its receptor?

A

. Insulin receptor Tyr kinase activity stimulated

. Induces Tyr phosphorylation of various insulin receptor substrates (IRS)

32
Q

IRS protein types

A

. IRS-1, IRS-2 widely expressed
. IRS-3 found in adipose tissue, pancreatic beta cells, and possible liver
. IRS-4: thymus, brain, kidney

33
Q

What can Tyr phosphorylated IRS proteins bind?

A

. SH-2 containing proteins including ones activated by Ras
. STATs
. Ser kinase
. PI-3 kinase
. Activation of Ras and of STAT signaling leads to regulation of transcription of specific genes

34
Q

Activation of PI-3 kinase followed by activation of downstream kinases promotes _____

A 
. Glucose transport 
. Protein synthesis 
. Glycogen synthesis 
. Cell proliferation
. Cell survival in various cells and tissues
35
Q

Molecules that signal target cells using NISS and MISS

A 
. Sex steroid hormones
. Glucocorticoids 
. Mineralcorticoids
. Vit. A and D 
. Retinoids 
. Thyroid hormones
36
Q

Nuclear-initiated steroid signaling (NISS)

A

. Classical steroid signaling
. Steroid hormones leave circulation and cross barrier of plasma membrane of target cell to reach receptor
. Once inside plasma membrane, steroid encounters receptor in cytosol or nucleus
. Hormone binding modifies receptor enabling it to regulate transcription of specific genes

37
Q

Ligand-activated transcription factors

A

Intracellular steroid hormone receptors

38
Q

Membrane-initiated steroid signaling (MISS)

A

. Steroid receptors localized to plasma membrane
. Causes rapid effects of steroid hormones that occur w/in sec. to min.
. Promotes modification of existing proteins and doe snot require synthesis of new proteins like NISS does

39
Q

MISS receptor structure

A

. Same protein structure as intracellular steroid hormones but localized to caveolae

40
Q

General mechanism of MISS

A

. Steroid binds
. Membrane receptor assoc. w complex of signaling proteins (G proteins, growth factors receptors, Src, and Ras)
. Protein kinases function in G protein signaling and PI=3 kinase can be activated
. Phosphorylation of target proteins causes rapid biological response by the cell

41
Q

What does insulin inhibit?

A

. Glucose uptake
. Glycogen synthesis
. Protein synthesis

42
Q

epinephrine role in metabolism

A

. Stimulates liver to convert glycogen to glucose using cAMP as second messenger

43
Q

PKA structure

A

. 2 regulatory subunits bound to 2 catalytic subunits when inactive
. When cAMP binds the subunits separate and catalytic subunit phosphorylates Ser and Thr residues in proteins substrates

44
Q

DAG location

A

Inside membrane (IP3 is free)

45
Q

PKC activation

A

. needs DAG and Ca2+

46
Q

IP3 releases what and what is it’s roel?

A

. Ca via binding receptors on ER
. Ca acts as second messenger
. Ca binds to calmodulin and Ca-Calmodulin activates cellular proteins

47
Q

Intracellular receptor for steroid structure

A 
. NH2-terminal genre regulatory domain
. DNA binding domain
. Hinge region (folded for activation, flat for inactivation) 
. Hormone binding site
. COOH-terminal hormone binding region

Biochemistry (64 decks)

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