Unit 3: Chapter 13

Question 1

Signal transduction cascade commonalities:

Answer 1

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

Question 2

Since signal transduction is on, it needs to …

Answer 2

turn off

Question 3

How does cancer cells indicate something wrong with signal transduction?

Answer 3

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

Question 4

Signaling molecules

Answer 4

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

Question 5

After signal molecule binds to receptor what happens

Answer 5

Receptor changes conformation

Question 6

What are the two types of receptors?

Answer 6

1. Cell surface receptors
2. Intracellular receptors

Question 7

Location of receptor depends on what

Answer 7

Whether signaling molecule is polar or nonpolar

Question 8

Cell Surface receptors

Answer 8

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

Question 9

Intracellular receptors

Answer 9

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

Question 10

Target cells detect signal using what

Answer 10

Receptor protein

Question 11

Second messengers

Answer 11

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

Question 12

What determines whether a cell responds to a signaling molecule?

Answer 12

Presence of receptor proteins of target cell

Question 13

3 Major classes of cell surface receptors

Answer 13

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

Question 14

Kinase

Answer 14

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

Question 15

Phosphatase

Answer 15

enzyme that catalyzes dephosphorylation

Question 16

GTPase

Answer 16

enzyme catalyzes hydrolysis of GTP to GDP and inorganic phosphate

Question 17

Cyclic AMP phosphodiesterase

Answer 17

continuously converts cAMP to AMP

Question 18

GPCR: G Protein Coupled Receptors

Answer 18

• 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

Question 19

Activation of protein kinase A by G Protein pathway

Answer 19

• 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

Question 20

In epinephrine signal transduction pathway, upon activation to receptor

Answer 20

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

Question 21

How do G proteins reset?

Answer 21

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

Question 22

How to shut down epinephrine initiated pathway

Answer 22

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

Question 23

How to reset GTP alpha subunit?

Answer 23

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

Question 24

Phosphoinositide pathway to generate IP3 and DAG

Answer 24

• 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

Question 25

Receptor dimerization may result in

Answer 25

Tyrosine kinase recruitment

Question 26

Human growth hormone receptor

Answer 26

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

Question 27

When does receptor dimerize

Answer 27

Upon hormone binding to receptor

Question 28

Which signal transduction pathways use G Protein Coupled Receptors?

Answer 28

Activation of Protein kinase A with epinephrine IP3 and DAG Pathway

Question 29

Which signal transduction pathways use receptor Tyrosine Kinase?

Answer 29

JAK2 and STATS pathway EGF Signaling Insulin Signaling

Question 30

Receptor Tyrosine Kinase activates JAK2/ STAT5 Pathway

Answer 30

- 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 -

Question 31

STAT5

Answer 31

Regulator of gene expression and further propagates the signal

Question 32

EGF Signaling Pathway Through Receptor Tyrosine Kinase

Answer 32

- 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

Question 33

If Ras protein has GDP, it is

Answer 33

Inactive

Question 34

SOS

Answer 34

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

Question 35

If Ras protein has GTP, it is

Answer 35

Active

Question 36

Ras protein

Answer 36

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

Question 37

Rho (subfamily of Ras)

Answer 37

reoorganizes cytoskeleton through serine or threonine protein kinases

Question 38

Rab (subfamily of Ras)

Answer 38

plays a key role in secretory and endocytotic pathways

Question 39

Insulin signaling pathway through receptor tyrosine kinase

Answer 39

- 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

Question 40

Insulin

Answer 40

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

Question 41

Which pathway is the receptor already a dimer?

Answer 41

Insulin signaling pathway