Signaling

Question 1

Ligands (primary messengers):

Answer 1

hormones (insulin, glucagon), growth factors, proteins, small molecules (histamine or epinephrine)

Question 2

Receptors:

Answer 2

Tyrosine kinase/phosphatase receptors
G protein-coupled receptors (GPCR)

Question 3

G proteins (transduction):

Answer 3

Heterotrimeric (3 subunits)
Monomeric (1 subunit)

Question 4

Effectors & 2nd messengers (transduction):

Answer 4

Effectors are usually proteins
2nd Messengers usually small mol like calcium, IP3, DAG, etc.

Question 5

Ligands (Agonists)

Answer 5

small molecules that bind to specific receptors. Variety of shapes and sizes.

Question 6

Membrane Receptor Types

Answer 6

G protein-coupled receptors (GPCR); aka
7TMR, serpentine receptors & RTK RTP

Question 7

G protein-coupled receptors (GPCRs)

Answer 7

Epinephrine, Insulin

Question 8

Receptor Tyrosine Kinases (RTKs)

Answer 8

Epidermal Growth Factor

Question 9

Physiological Responses Downstream of GPCRs

Answer 9

Cell growth and differentiation
RTKs (Glucose met.,Cell growth)

Question 10

GPCRs Bind Ligands Within

Answer 10

the TM Domains

Question 11

“Infamous” GPCR Drugs and Agonists

Answer 11

Heroin, Morphine:m-Opioid Receptor
(endorphins)
LSD:5-HT Receptor (Serotonin)
THC:CB1, CB2 (Cannabinoid) Receptors

Question 12

Agonists

Answer 12

ligands that directly bind GPCRs
and stimulate a physiological response that is beneficial for the patient. e.g. albuterol (bAR, asthma), THC (CB1-2), etc.

Question 13

Antagonist

Answer 13

ligands that also directly bind GPCRs but do not stimulate a response. This class works by competing with endogenous ligands e.g. antihistamines, b-blockers, curare (nicotinic acetylcholine receptor), clozapine (dopamine receptors) and caffeine (A2 adenosine receptor).

Question 14

G Proteins (GTPases)

Answer 14

So named because they bind guanyl nucleotides

Question 15

Heterotrimeric

Answer 15

(3 subunits: a, b, g),
defined by the a subunit families:
4 = Gai, Gas, Gaq, & Ga12/13

Question 16

Monomeric (1 subunit related to Ga)

Answer 16

Ras (rat sarcoma)

Question 17

Heterotrimeric G Protein Quaternary Structure

Answer 17

A ribbon diagram shows the relation between the three subunits. In this complex, the α subunit (gray and purple) is bound to GDP. Notice that GDP is bound in a pocket close to the surface at which the α subunit interacts with the βγ dimer. (B) A schematic representation of the heterotrimeric G protein

Question 18

Heterotrimeric G Proteins Directly Contact

Answer 18

GPCRs

Question 19

Membrane localization

Answer 19

a and g subunits are lipid modified

Question 20

Effectors (Targets of G Proteins)

Answer 20

Adenylate cyclases
(downstream of Gas)
Phospholipases (PLCb is downstream of Gaq and bg)

Question 21

Adenylate Cyclase is Stimulated by

Answer 21

G alpha s

Question 22

Common 2nd Messengers

Answer 22

IP3 and DAG

Question 23

Phospholipase C (PLC) Cleaves

Answer 23

PIP2 to generate IP3 and DAG

Question 24

EF Hands are Protein Domains that Bind

Answer 24

Ca++

Question 25

Ca++ Regulates

Answer 25

Downstream Enzymes Directly (PKC) or via Calmodulin (CaM) Kinase

Question 26

ionic and hydrophobic interactions between

Answer 26

CaM kinase and Calmodulin