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Biochemistry > Unit 3: Chapter 13 > Flashcards

Unit 3: Chapter 13 Flashcards

1
Q

Signal transduction cascade commonalities:

A
  1. release of primary messenger due to physiological circumstance
  2. receptor receives primary messenger
  3. relay of primary messenger to inside cell by intracellular second messenger
  4. activation of effector molecules by second messenger to result in physiological response
  5. Termination of signal cascade
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2
Q

Since signal transduction is on, it needs to …

A

turn off

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3
Q

How does cancer cells indicate something wrong with signal transduction?

A

Cancer cells is uncontrolled cell division and indicates signal transduction is always on

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4
Q

Signaling molecules

A

Primary messenger aka ligand
Produced by signaling cells and bind to receptor on or in target cell

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5
Q

After signal molecule binds to receptor what happens

A

Receptor changes conformation

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6
Q

What are the two types of receptors?

A
  1. Cell surface receptors
  2. Intracellular receptors
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7
Q

Location of receptor depends on what

A

Whether signaling molecule is polar or nonpolar

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8
Q

Cell Surface receptors

A
  • Integral membrane receptors (transmembrane)
  • Bind to signaling molecules on extracellular domain of receptor of target cell membrane
  • Signal does not need to cross membrane
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9
Q

Intracellular receptors

A

Nonpolar signaling molecules can cross target cell membrane and bind to receptor in cytosol or nucleus

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10
Q

Target cells detect signal using what

A

Receptor protein

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11
Q

Second messengers

A

Relay info from receptor signal molecule complex and amplify signals inside the cell

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12
Q

What determines whether a cell responds to a signaling molecule?

A

Presence of receptor proteins of target cell

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13
Q

3 Major classes of cell surface receptors

A
  1. Seven transmembrane helix receptors (G-Protein coupled receptors aka GPCRs) associated with heterotrimeric G proteins
  2. Dimeric membrane receptors that recruit tyrosine kinase
  3. Dimeric protein receptors that are protein tyrosine kinase
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14
Q

Kinase

A

enzyme that transfers phosphate group ATP to target molecule (catalyze phosphorylation)

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15
Q

Phosphatase

A

enzyme that catalyzes dephosphorylation

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16
Q

GTPase

A

enzyme catalyzes hydrolysis of GTP to GDP and inorganic phosphate

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17
Q

Cyclic AMP phosphodiesterase

A

continuously converts cAMP to AMP

18
Q

GPCR: G Protein Coupled Receptors

A
  • 7 membrane
  • Mediate a host of biological functions by responding to a variety of signal molecules aka ligands
  • Binding of ligand occurs outside the cell induces receptor change conformation which is detected inside the cell
  • attractive target for development of drugs
19
Q

Activation of protein kinase A by G Protein pathway

A
  • Beta adrenergic receptor (type of GPCR) binds to epinephrine (first messenger) which changes conformation that is detected inside the cell by the G protein
  • Trimeric G protein is the partner in the coupled rxn
  • When signal is off G protein has GDP and is trimeric
  • When signal is on G protein changes conformation and how has GTP and disassociates to alpha subunit
  • Next target is adenylate cyclase (transmembrane embedded integral protein)
  • Adenylate cyclase activates cyclic AMP (second messenger) which activates protein Kinase A
  • Protein Kinase A will add phosphate to more target cells
20
Q

In epinephrine signal transduction pathway, upon activation to receptor

A

alpha subunit dissociates by beta gamma dimer and exchange GDP to GTP

21
Q

How do G proteins reset?

A

Reset themselves through GTP Hydrolysis
GTP + H20 –> GDP + Pi
G protein to be inactive

22
Q

How to shut down epinephrine initiated pathway

A
  1. G alpha protein binds to GDP to reassociate with beta gamma units terminate activity of G protein
  2. Cyclic AMP phosphodiesterase converts cAMP to AMP so protein kinase not activated
  3. Epinephrine beta adrenergic receptor interaction is reversal, no signal binding to receptor does not initiate signal pathway
23
Q

How to reset GTP alpha subunit?

A

GTP alpha subunit hydrolyzes to GDP and reassociates with beta gamma subunits for signal to turn off

24
Q

Phosphoinositide pathway to generate IP3 and DAG

A
  • G protein coupled receptors activate phosphoinositide pathway generating IP3, DAG, Ca2+
  • G alpha protein activates phospholipase C which cleaves membrane lipid PIP2 into 2 second messengers: IP3 and DAG
  • Diaglycerol (DAG) never diffuses and stay in membrane
  • IP3 diffuses into cytoplasm and bind to IP3 gated channel (receptor) in ER which allows for calcium channels top open
  • DAG and Ca2+ activate protein kinase C
25
Q

Receptor dimerization may result in

A

Tyrosine kinase recruitment

26
Q

Human growth hormone receptor

A

Monomeric integral membrane protein with an extracellular and intracellular domain joined intramembrane alpha helix

27
Q

When does receptor dimerize

A

Upon hormone binding to receptor

28
Q

Which signal transduction pathways use G Protein Coupled Receptors?

A

Activation of Protein kinase A with epinephrine
IP3 and DAG Pathway

29
Q

Which signal transduction pathways use receptor Tyrosine Kinase?

A

JAK2 and STATS pathway
EGF Signaling
Insulin Signaling

30
Q

Receptor Tyrosine Kinase activates JAK2/ STAT5 Pathway

A
  • Dimerizatrion of extracellular domains of receptor brings together intracellular domains associated with JAKS2
  • Each JAK phosphorylates its partners (cross phosphorylat ion) on a tyrosine residue to activate 2 kinases
  • ## Activated kinases phosphorylate targets including STAT5
31
Q

STAT5

A

Regulator of gene expression and further propagates the signal

32
Q

EGF Signaling Pathway Through Receptor Tyrosine Kinase

A
  • EGF Signaling binds to EGF receptor for dimerization to occur and cross phosphorylation by tyrosine kinase
  • Tyrosine Kinase adds phosphate to tyrosine
  • Grb-2 protein is activated
  • SOS connects GP2 and GDP and stimulate exchange GDP for GTP in Ras protein
  • Ras protein becomes active with GTP
  • Last protein go downstream to activate more cells
33
Q

If Ras protein has GDP, it is

A

Inactive

34
Q

SOS

A

Adaptor protein connecting signals togehter of Grb-2 and GDP
Stimulates exchange GDP for GTP in Ras protein

35
Q

If Ras protein has GTP, it is

A

Active

36
Q

Ras protein

A

Monomeric G protein (Single polypeptide chain)
intrinsic
has GTPase activity which controls signal duration
Regulates cell growth through serine or threonine protein kinases

37
Q

Rho (subfamily of Ras)

A

reoorganizes cytoskeleton through serine or threonine protein kinases

38
Q

Rab (subfamily of Ras)

A

plays a key role in secretory and endocytotic pathways

39
Q

Insulin signaling pathway through receptor tyrosine kinase

A
  • Insulin receptor tyrosine kinase is ALREADY DIMER (even in absence of insulin)
  • Insulin binding causes change in structure which results in cross phosphorylation by 2 kinase domains
  • activated kinase of insulin receptor phosphorylates IRSs
  • phosphorylated IRSs covey insulin signal
  • phosphoinositide 3- kinase binds to IRS and phosphorylates PIP2 to PIP3
  • PIP3 activates PIP3 dependent protein kinase (PDK1)
  • PDK1 phosphorylates and activates kinase Akt by ATP to ADP
  • Akt phosphorylates enzymes that control GLUT4, increasing glucose uptake, and convert glucose into glycogen
40
Q

Insulin

A

Hormone protein that is secreted when blood is rich in glucose
Biochemical signal for fed state
A receptor tyrosine kinase
Consists of 2 polypeptide chaisn linked by disulfide bonds

41
Q

Which pathway is the receptor already a dimer?

A

Insulin signaling pathway

Biochemistry (17 decks)

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