Lecture 8

Question 0

Paracrine signaling

Answer 0

Signal acts on a neighboring cell (NO2)

Question 1

Endocrine signaling

Answer 1

Transported through circulation to target cell (hormones)

Question 2

Autocrine signaling

Answer 2

Cell responds to its own signal

Question 3

Neurotransmitter

Answer 3

Type of paracrine signaling

Bind to membrane receptors on cell surface

Question 4

What are examples of neurotransmitters?

Answer 4

Ach
Amino Acids (Glu, Asp, Gly)
GABA
Monoamines

Question 5

What are the two types of monoamines?

Answer 5

Catecholamines (dopamine, norepinephrine, epinephrine)

Indoleamine (serotonin)

Question 6

What are examples of non-neurotransmitters?

Answer 6

Insulin, Glucagon, Pituitary Trophic Hormones

Question 7

What are examples of growth factors?

Answer 7

Nerve, epidermal, and platelet-derived growth factor

Question 8

What type of messengers bind extracellularly?

Answer 8

Neurotransmitters
Non-neurotransmitters
Growth factors

Question 9

What messengers bind intracellularly?

Answer 9

Steroids

Non-steroids

Question 10

What are examples of steroids?

Answer 10

Testosterone
Estrogen
Progesterone
Corticosteroids

Question 11

What are examples of non-steroids?

Answer 11

Thyroid hormone
Vitamin D3
Retinoids

Question 12

What are the different receptor classes?

Answer 12

G protein-coupled receptors
Tyrosine kinase receptors
Cytokine receptors

Question 13

What are the characteristics of G protein-coupled receptors?

Answer 13

7 membrane-spanning helices
NH2 is extracellular and binds to ligand
COOH is intracellular and interacts with G protein
Heterotrimeric (alpha, beta, gamma)
Alpha interacts with G protein

Question 14

What are the functions of G protein-coupled receptors?

Answer 14

Regulate enzyme/ion channels
Largest family responsible for odor detection
Control effectors altering activity of second messengers (cAMP, DAG)

Question 15

When a ligand binds to a G protein-coupled receptor, what happens intracellularly?

Answer 15

GDP is exchanged for GTP on alpha subunit
Alpha subunit breaks away from Beta/Gamma dimer
Alpha subunit acs on effectors or activates other G proteins to amplify signal
Effector stimulates GTPase activity of alpha subunit

Question 16

How does an alpha subunit for G protein get activated?

Answer 16

A GDP is exchanged for a GTP resulting in activation

Question 17

What are the characteristics of enzyme-linked receptors?

Answer 17

Single pass transmembrane proteins
Associated with intracellular effector capable of generating intracellular signal
C-terminal undergoes ligand-induced dimerization & receptor autophosphorylation

Question 18

What are the classes of enzyme-linked receptors?

Answer 18

Guanylyl cyclase activity receptors (increase intracellular [cGMP])
Phosphorylation/dephosphorylation catalysts for intracellular signaling proteins

Question 19

What are the characteristics of tyrosine kinases?

Answer 19

Phosphorylation of tyrosine in catalytic domain increase protein kinase activity
Phosphorylation of tyrosine out of catalytic domain creates binding sites for other proteins that transmit signals downstream (amplifies incoming signal)

Question 20

What are the characteristics of cytokine receptors?

Answer 20

No cytosolic catalytic activity
Associated with JAK
Can’t autophosphorylate

Question 21

What are characteristics of non-receptor protein-tyrosine kinases?

Answer 21

Belong to JAK and Src families
Ligand binding induces dimerization
Dimerization of receptor leads to dimerization of JAK’s which autophosphorylate and then phosphorylate the receptor
Phosphorylation of receptor provides binding sites for recruitment of downstream signaling molecules (STAT’s)

Question 22

What are characteristics of the cAMP pathway?

Answer 22

ATP converted to cAMP
cAMP degraded to AMP
cAMP binds to cAMP dependent protein kinase (Kinase A)
Kinase A moves into nucleus
Kinase A binds to CREB (transcription factor) which is bound to CRE (cAMP response element)
Turns on specific genes dependent on transcription factor involved

Question 23

Describe the JAK-STAT pathway

Answer 23

JAK’s activate when cytokine receptors dimerize, then JAK’s come together and autophosphorylate
(These JAK’s phosphorylate receptors)
Receptors have binding sites for STAT’s
STAT is phosphorylated by JAK and forms dimer which translocates into nucleus and activates transcription

Question 24

T/F: All STAT dimers activate the same DNA sequences

Answer 24

False, different STAT dimers activate different DNA sequences

Question 25

Describe the ERK-MAP kinase pathway

Answer 25

Ligand binds to membrane growth factor
Ras replaces GDP with GTP and interacts with Raf kinase
Raf phosphorylates and activates MEK
MEK activates MAPK(ERK) which moves into nucleus and phosphorylates Elk-1 (transcription factor)

Question 26

What are characteristics of hedgehog pathway?

Answer 26

Receptor is transmembrane protein called “Patched”

Inhibits a second transmembrane protein called “Smoothened”

Question 27

What does the hedgehog pathway play important role in?

Answer 27

Determination of cell fate during embryonic development

Regulation of proliferation of stem cells into adult tissues

Question 28

Describe the hedgehog pathway

Answer 28

Binding of hedgehog inhibits “Patched”

Inhibition of “Patched” leads to activation of “Smoothened” and activation of transcription from Gli

Question 29

Describe the Wnt proteins

Answer 29

Growth factors
Bind to receptors of Frizzled and LRP families
Signals from Frizzled and LRP stabilize beta-catenin which is a transcriptional activator

Question 30

Describe the notch pathway

Answer 30

Cell-cell interaction during development (paracrine)
Single transmembrane domain
Ligand binding leads to proteolytic cleavage of notch
Intracellular domain moves into nucleus and converts transcription factor CSL from repressor to activator