Cell Signaling

Question 1

What is the general structure of RTK’s?

Answer 1

Single pass transmembrane proteins with extracellular ligand binding domain and intracellular protein kinase domain

Question 2

What common critical functions do RTK’s perform?

Answer 2

Signal pathways important for cell proliferation and tissue repair

Question 3

Name four signaling protein domains that recognize P-RTK and what they recognize

Answer 3

SH2 and PTB: p-Tyr
SH3: proline-rich
PH: lipids (PIP2, PIP3)

Question 4

Why is it important that each RTK contains several p-tyr residues?

Answer 4

It can interact with several different SH2 proteins at the same time, simultaneously activating different pathways

Question 5

Name the major players in the MAPK pathway in order. Which one is the GTP/GDP exchange factor? Which one requires the GEF activity?

Answer 5

GRB2
SOS (GEF)
Ras (requires GEF activity of SOS to attach to cell membrane and activate)
Raf
MEK (phosphorylated by RAF)
MAPK/ERK (phosphorylated by MEK)

Question 6

40% of solid tumors contain a mutation in ____

Answer 6

Ras

Question 7

What are four ways to terminate the MAPK pathway?

Answer 7

Spontaneous hydrolysis of GTP by Ras
Ras-GAP hydrolyzes Ras bound GTP
Protein phosphatases that deactivate every component of the pathway
Internalization of the receptor

Question 8

Name the sequence of events in the PI3K pathway

Answer 8

PI3K phosphorylates PI
PI3K binds RTK (PIP2) and produces PIP3
Cytoplasmic AKT is recruited and activated by PIP3
AKT is phosphorylated by PDPK1
AKT phosphorylates its targets

Question 9

What does TSC1/TSC2 complex do? What happens when AKT acts on it?

Answer 9

TSC1/2 is a GTPase activating protein (GAP) for Rheb. When it is phosphorylated by AKT it is inhibited, causing an increase in GTP bound Rheb

Question 10

What activates mTORC1?

Answer 10

Rheb/GTP

Question 11

Activated mTORC1 results in ____

Answer 11

upregulated protein translation and increased cell growth

Question 12

Name an mTORC1 inhibitor

Answer 12

rapamycin

Question 13

How is the PI3K signal terminated?

Answer 13

PTEN phosphates dephorsphorylate PI3K

Question 14

Briefly describe the PLCg pathway

Answer 14

PLCg hydrolyzes PIP2 and produces IP3 and DAG
IP3 binds the ER and releases calcium into the cytoplasm
DAG activates PKC

Question 15

Describe the general structure of G protein coupled receptors

Answer 15

They are 7-pass transmembrane proteins with an extracellular N terminus and cytosolic C terminus

Question 16

Describe the general structure of G proteins

Answer 16

They consist of three subunits, alpha, beta, gamma subunits. The alpha subunit has RAS-like GTPase activity. Beta and gamma form a complex

Question 17

Describe the action of the G protein alpha subunit

Answer 17

GPCR facilitates exchange of GDP for GTP on the alpha subunit. This causes alpha to dissociate and bind its downstream targets

Question 18

How is the GPCR pathway signal terminated?

Answer 18

Alpha hydrolyzes its bound GTP with the help of RGS and reunites with beta-gamma

Question 19

How is cAMP concentration regulated?

Answer 19

Changing the concentration of adenylyl cyclase or phosphodiesterase

Question 20

cAMP binds to and activates ___

Answer 20

cAMP-dependent protein kinase or protein kinase A (PKA)

Question 21

Name some PKA substrates

Answer 21

phosphorylase kinase
glycogen synthase
hormone sensitive lipase
perilipin
CREB

Question 22

IP3 is important for control of what intracellular ion via what messenger protein?

Answer 22

Calcium via calmodulin

Question 23

Name two ways GPCRs can be regulated

Answer 23

Phosphorylation by PKA and PKC

Phosphorylation by GRKs

Question 24

What type of signaling pathway do vision, smell, and taste use?

Answer 24

GPCR’s

Question 25

Describe the sequence of events of rod cell signaling

Answer 25

Receptor rhodopsin activated by light
Rhodopsin activates G protein transducin alpha subunit
GTP-alpha subunit of transducin activates cGMP PDE, decreasing concentration of cGMP
cGMP gated channels close, causing hyperpolarization

Question 26

What is the G protein specific to the smell pathway?

Answer 26

Golf

Question 27

What are the GPCR’s responsible for umami, sweet, and bitter taste?

Answer 27

T1R1/T1R3
T1R2/T1R3
T2R

Question 28

What G protein is specific to the taste pathway?

Answer 28

Gustducin