Cell Signaling Quiz 4

Question 1

Inositol phospholipids

Answer 1

a lipid composed of a phosphate group, two fatty acid chains, and one inositol molecule. It belongs to the class of phosphatidylglycerides
Is typically found as a minor component on the cytosolic side of eukaryotic cell membranes.

Question 2

What does PIP2 make when cleaved?

Answer 2

Makes DAG and another molecule that when exposed to water makes IP3
Leads to calcium release hen it works with kinase C (via DAG recruiting it) and opening of calcium channels (via IP3)

Question 3

PIP, PIP2, PIP3

Answer 3

With the use of P13K and PTEN they can all undergo reactions to become one another
They do this to change their functions

Question 4

PI (3,4,5)P3

Answer 4

Activates Akt (protein kinase B) which works with cell survival

Question 5

PLC in bacteria

Answer 5

Used to lyse cell membrane un our cells

Question 6

PLCs

Answer 6

Six isotypes in animals
Thirty types in mammals
Most need Ca2+ to function properly

Question 7

PLC-beta

Answer 7

4 genes
PLCB1, PLCB2, PLCB3, PLCB4

Question 8

PLCB1

Answer 8

Activated by Galphaq1, G alpha

Question 9

PLCB2

Answer 9

Same Galpha as PLCB1
Can also be activated by Gbetagamma

Question 10

PLCB3

Answer 10

Same Galpha as PLCB1
Can also be activated by Gbetagamma

Question 11

PLCB4

Answer 11

Not sure but is localized to ? and has two isoforms

Question 12

PLC-gamma

Answer 12

2 genes: PLCG1 and PLCG2
PLC-gamma is activated by RTK, not by proteins

Question 13

PLC-delta

Answer 13

Three genes: PLCD1, PLCD2, PLCD3
PLCD1=skin homeostasis
PLCeta and PLCzeta also exist

Question 14

PLC structure

Answer 14

Have common domains and variability outside of these:

PH: binds inositol phospholipids

EF-hand domains: helix-loop-helix structure. Used to bind Ca2+ ions

TIM-Barrel domain: alternative alpha helices and beta sheets which forms a donut structure: catalytic domain

XY linkers: Splits catalytic domain

C2: Binds Ca2+ membranes

PICTD: Galphaq binding site

CTD linker: unconserved

Distal CTD: Contributes to Galphaq and membrane binding

Question 15

Different inositol phospholipids are used for?

Answer 15

By having different kinases can make massive different molecules used for signaling
It is easy to P’late and is therefore easy to switch rxn off
Therefore can modulate how long/when phosphosinositol can be used

Question 16

What role does IP3 have?

Answer 16

Used to release Ca2+
Gets P’lated and reverses its action and uptakes Ca2+ back into SR
Therefore calcium signal is short lived

Question 17

Purposes of many types of DAG

Answer 17

Activate PKC
Several pathways
Do not understand how it is degraded
Not always on PM. Is on nuclear envelope so possibly the nucleus stores Ca2+?

Question 18

Difference between sphingolipids and phospholipids?

Answer 18

Use sphingosine instead as a base molecule and not a glycerol

Question 19

Arachidonic acid

Answer 19

Production of prostoglandins

Question 20

GTP binding proteins

Answer 20

Switch with GDP and GTP bound states
Are on when GTP is bound and are off when GDP is bound

Question 21

Which concentration do you want more for GTP binding proteins? GDP or GTP

Answer 21

GTP
Therefore you can kick out GDP for nucleotide exchange

Question 22

How do we go from GTP to GDP?

Answer 22

Hydrolysis reaction to occur

Question 23

How do we go from GDP to GTP?

Answer 23

Nucleotide exchange

Question 24

Do you want a fast or slow reaction for GTP binding proteins?

Answer 24

Want a slow reaction rate for signaling path to be slow
Half-time can be hours

Question 25

GTP and GDP affinity for GTP binding proteins?

Answer 25

Both high so you can get a consistent signal that can be transduced Helps because then the signal will not be accidently switched on or off

Question 26

Guanine nucleotide exchange factors (GEFs)

Answer 26

Takes GTP and turns on GTP binding protein

Question 27

GTPase activating proteins (GAPs)

Answer 27

Remove phosphate from GTP binding protein to turn off GTP binding protein

Question 28

GTP binding proteins are

Answer 28

GTPases GAP will increase efficiency of GTPase

Question 29

The structural mechanisms of GTP binding proteins?

Answer 29

With ADP: GDP binds in the center of tweezers of the protein Gly60 on switch II, and Thr35 on switch I Gly60 and Thr35 is where the target protein (enzyme most of the time) is going to bind to bring them inwards when activated Without ATP: Target protein attaches to Gly60 and Thr35 with P attaching to target protein as well

Question 30

GTP binding proteins

Answer 30

Monomeric GTP binding protein "Small GTPases" Heterotrimeric GTP binding proteins "G proteins" These are the two classes of GTP binding proteins Contain alpha, beta, and gamma polypeptide Alpha polypeptide is GTP binding subunit ~150 small GTPases

Question 31

Ras

Answer 31

Proliferation and differentiation Induce tumor formations

Question 32

Rho

Answer 32

Cell shape

Question 33

Rab

Answer 33

Vesicular trafficking Vesicle target docking

Question 34

Arf

Answer 34

Vesicular trafficking Used at start of things Vesicle formation

Question 35

Ran

Answer 35

Nuclear import/export

Question 36

G proteins

Answer 36

Fewer in number 16aplha genes Galphas, Galpha1, Galphaq/11, Galpha12/13

Question 37

Lots of GPCRs

Answer 37

Receptors that activate G proteins

Question 38

GPCR specificity and G and effector proteins that come after it. Do the other proteins need to be specific?

Answer 38

As long as we can ensure the right effector is activated in response to signal, G protein uniqueness is less important Cell specific expression of GPCR/effector or we could have specific localization of the GPCR/effector on plasma membrane Therefore will not accidently activate something else

Question 39

What activates and deactivates G proteins

Answer 39

~GPCR (GEFs) activate them ~20 G proteins ~RGS (GAPS, Regulations of G protein signaling)

Question 40

What activates and deactivates Rho?

Answer 40

~80 Rho GEFs activate ~20 Rho ~70 Rho GAP deactivate ~20 Rho

Question 41

Are GTP binding proteins in a signaling pathway the center of the pathway?

Answer 41

GTP binding protein in the center is not really big picture of pathway

Question 42

Mechanisms of GEFs

Answer 42

They go to the point where they bind to tweezers and Phosphate. Opens the wings and GTP/GDP is released then new molecule can bind to GTP binding protein

Question 43

What does GAP do to molecule

Answer 43

GAP orients molecules to drive hydrolysis rxn. Line up H2O, GTP and GTPase Single A.A. is disordered that is put into ordered state Arginine finger to neutralize phosphate for rxn. to occur

Question 44

GD1

Answer 44

Stop dissociation of GDP for GTP

Question 45

GD1 displacement factors

Answer 45

kicks GD1 off

Question 46

GoLoco

Answer 46

Influence retrimerization of beta-gamma protein. Stop it.