Cell Signaling I (CH15)

Question 1

autocrine signaling

Answer 1

acts on the same cell that produced the signal (i.e. growth factors, cytokinesis, and tumor cells)

Question 2

endocrine signaling

Answer 2

acts on distant cells (i.e. hormones)

Question 3

paracrine signaling

Answer 3

acts on close cells (i.e. neurotransmitters and growth factors)

Question 4

cell-cell signaling

Answer 4

membrane attached signals bind receptor of adjacent cell

Question 5

what determines the specificity of cell signaling?

Answer 5

cell type specificity, down stream effectors, binding specificity, and effector specificity

Question 6

second messengers

Answer 6

Low molecular weight molecules with short half-life that increase or decrease as a result of ligand binding to activate downstream proteins

Question 7

the 4 second messengers

Answer 7

cAMP, cGMP, DAG, IP3

Question 8

cAMP

Answer 8

activates protein kinase A (PKA)

Question 9

cGMP

Answer 9

activates PKG

Question 10

DAG (function)

Answer 10

activates PKC

Question 11

IP3 (function)

Answer 11

opens Ca2+ channels of endoplasmic reticulum

Question 12

classes of GTPases

Answer 12

trimeric G-proteins

monomeric G-proteins

Question 13

trimeric G-proteins

Answer 13

made of 3 proteins (one of which is GTP binding (Gα)) and associate with G-protein coupled receptors

Question 14

monomeric G-proteins

Answer 14

part of the Ras superfamily

and link indirectly to receptors by adaptor proteins

Question 15

kinase

Answer 15

enzyme that phosphorylates proteins (adds phosphate)

Question 16

phophotase

Answer 16

dephosphorylates proteins (removes the phosphate)

Question 17

cell type specificity

Answer 17

different forms of receptors that bind the same ligand but elicit a different response

Question 18

down stream effector specificity

Answer 18

cells express different effector molecules

Question 19

binding specificity

Answer 19

receptors bind a single molecule or family of molecules

Question 20

effector specificity

Answer 20

different cellular response to the binding of a signal molecule to a particular receptor for different cell types

Question 21

MAPK Pathway

Answer 21

surface receptor activates GEF, activates Ras-GDP to Ras-GTP, Raf > MEK > ERK
phosphorylation of transcription factor, change in gene expression

Question 22

a kinase can phosphorylate:

Answer 22

tyrosine or serine/threonine

Question 23

G-protein coupled receptor

Answer 23

has 7 membrane spanning regions with N-terminus on outside and C-terminus on inside of cell; has 4 extracellular segments for ligand interaction and 4 intracellular segments to interact with trimeric G-proteins

Question 24

G-protein structure and function

Answer 24

Gα and Gßγ subunit; transduce signals from the G-Protein Coupled Receptor to the Signal Transduction Pathways

Question 25

Gα

Answer 25

GTP binding; transduces signals in GTP bound state

Question 26

Gßγ

Answer 26

associates with Gα-GDP and dissociates from Gα- GTP; sometimes transduces signals

Question 27

adenylyl cyclase (structure)

Answer 27

6 multispan homodimeric effector protein; made of two α helices; both N and C-terminus on cytoplasmic face; has 2 catalytic domains on cytoplasmic face

Question 28

adenylyl cyclase (regulation)

Answer 28

associated with ß-Adrenergic receptor (binds epinephrine) & a Gsα (stimulatory) –> increases cAMP; associated with ß-Adrenergic receptor (binds PGE or adenosine) & Giα (inhibitory) –> decreases cAMP

Question 29

GPCR signal regulation

Answer 29

GPCR signal termination, Receptor Desensitization, ß-Arrestin Mediated Desensitization of GPCR

Question 30

GPCR signal termination

Answer 30

rapidly induce GTP hydrolysis; inhibits activation of adenylyl cyclase; bind Gsα to GTP (decreases affinity of ligand for receptor, causes dissociation); convert cAMP to 5’-AMP

Question 31

Receptor Desensitization

Answer 31

PKA can phosphorylate and inhibit GPCR

Question 32

ß-Arrestin Mediated Desensitization of GPCR

Answer 32

BARK protein phosphorylates cytoplasmic side of GPCR; Arrestin binds phosphorylated residues; Associated protein complex has various effects (i.e.clathrin induces endocytosis of receptor)

Question 33

How are IP3 and DAG generated?

Answer 33

Phosphatidylinositol undergoes phosphorylations to become PIP2 and cleaving by Phospholippase C to form IP3 (the headgroup) and DAG (the diacyl chains)

Question 34

How do IP3 and DAG transduce signals throughout cells?

Answer 34

a ligand binds and activates the GPCR
trimeric G-protein binds GPCR
Gα binds GTP and dissociates from Gßγ
Gα binds Phospholippase C
Phospholippase C cleaves PIP2 to form IP3 and DAG
IP3 moves to the ER and opens the gated Ca2+ channel
Ca2+ moves from the ER to the cytoplasm
Ca2+ in cytoplasm interacts with PKC
PKC binds DAG and phosphorylates various substrates
Ca2+ channel can also interact with plasma membrane Ca2+ channel to move Ca2+ in/out of the cell

Question 35

Epinephrine Signaling

Answer 35

epinephrine binds ß-adrenergic receptor
ligand binding changes receptor conformation
change in receptor conformation allows receptor to bind Gα of heterodimeric G-protein
activated receptor changes conformation of G α which releases GDP
binding of GTP to G α promotes its dissociation from G ß γ
G α binds and activates adenylyl cyclase
activated adenylyl cyclase produces cAMP
cAMP binds regulatory subunit of PKA, releasing catalytic subunits
PKA catalytic subunit travels to nucleus
PKA phosphorylates transcription factor CREB
Phosphorylated CREB binds CRE and promotes transcription

Question 36

MAPK

Answer 36

Map Kinase; the terminal kinase that phosphorylates transcription factors

Question 37

PKA (protein kinase A) structure

Answer 37

2 catalytic subunits and 2 dimerized regulatory subunits that bind to the catalytic subunits to prevent substrate binding; dissociation induced by cAMP

Question 38

GPCR Regulation of Ion Channels

Answer 38

Acetylcholine binds and activates muscarinic acetylcholine receptor; Receptor activates trimeric G-protein; Gßγ binds and opens K+ channel