Brainscape's Knowledge GenomeTM

Browse over 1 million classes created by top students, professors, publishers, and experts.


See full index

MoMF > Cell Signaling > Flashcards

Cell Signaling Flashcards

1
Q

Receptor Tyrosine Kinase (RKT)

A

Single pass transmembrane proteins with ligand binding domains outside the cell and protein kinase domain inside the cell

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
2
Q

What can RKT control?

A

rate of cell proliferation and growth with the exception of insulin
*insulin does not control cell growth but has the same receptors as cell growth ligands

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
3
Q

Cell growth receptor ligands for RKTs

A 
EGF (epidermal)
PDGF (platelet)
FGF (fibroblast) 
VEGF (vascular endothelial) 
CSF (colony stimulating factor)
IGF1 (insulin like growth factor)
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
4
Q

1st step of RKT signaling

A

Receptor dimerization due to ligand binding

*ligands can either be dimers or monomers that cause conformational changes in the receptor and its dimerization

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
5
Q

What happens after dimerization of the receptor?

A

Leads to self-phosphorylation of the receptor on multiple tyrosine residues

The kinase domain of one receptor subunit phosphorylates the tyrosine’s on the other subunit

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
6
Q

How does binding lead to dimerization?

A

Binding causes conformational changes which propagates thru the membrane and forces tyrosine kinases closer to each other

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
7
Q

SH2 Domains

A

Large protein domains that recognize phosphotyrosine and bind to the phosphorylated receptors at these sites

(can also recognize several amino acids C terminal side of the tyrosine)

-Y-X-X-hy-

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
8
Q

PTB Domains

A

recognize phosphorylated tyrosines and several AA at the N terminal side of the tyrosine

-N-P-X-Y-

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
9
Q

SH3 Domains

A

recognize proline rich sequences

-P-X-X-P-X

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
10
Q

PH Domains

A

recognize phosphorylated lipids

-PI3,4P2, PI3,4,5P3

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
11
Q

RKT and SH2 Domains

A

Binding of SH2 Domain proteins to the activated RKT leads to activation of different downstream pathways

Each RKT contains several P-Tyr and so it can interact with several different SH2 proteins at the same time

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
12
Q

what does the MAP Kinase pathway do?

A

An example of an RKT pathway

Mediates cell proliferation (increase in cell number) and cell growth (increase in cell size)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
13
Q

Ras- basic pathway

A

GTPase protein
Mutated Ras found in 30% of mammalian tumors

RasGTP RasGDP

Gap activates forward reaction and GEF activates reverse
Once RasGDP, need GEF to bring back the GTP b/c thru GEF Ras binds to GTP since [GTP] 100x more than [GDP] in the cell

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
14
Q

Plasma membrane Ras

A

Involved in signaling
Farnesyl is attachd to C terminal of Ras so that Ras is attached to plasma membrane thru this hydrophoic anchor

can also be attached via fatty acid residue

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
15
Q

G2B2

A

Adaptor protein

SH3-SH2-SH3 domains

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
16
Q

MAP kinase pathway

A

Binding of the SH2 domain of G2B2 to the active RKT leads to plasma membrane recruitment of protein SOS (via its SH3 domain)

SOS facilitates the binding of GTP to Ras which activates Ras (RasGTP) making it tethered to the cell membrane

Activation of MAP kinase pathway

Activate Raf recruits Mek thru phosphorylation

Mek phosphorylates ERK

ERK dimerizes and is translocated to the nucleus where it phosphorylates transcription factors and activates transcription of early response genes

Products of these activated genes stimulate expression of other genes required to progress through the cell cycle

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
17
Q

SOS

A

GTP/GDP exchange factor for Ras

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
18
Q

Raf

A

Serine threonine kinase which is activated at the PM when

1) Ras binds to the PM
2) dimerization and phosphorylation occurs

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
19
Q

PI3K

A

Phosphatidyl Inositol 3-Kinases are lipid kinases that phosphorylate PI

PI is the ubiquitous component of the membrane

Involves downstream protein synthesis and cell growth

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
20
Q

PI3K 1A

A

Has 2 SH2 domains
Binds P-Tyr domains

1) regulatory subunit: p85
2) catalytic subunit: p110

p85 inhibits the activity of p110
under basal conditions, this enzyme is not active

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
21
Q

PI3K pathway

A

PI3K binds to two P-Tyr domains in the active RTK –> changes conformation of the enzyme –> activates and produces PIP3 in the plasma membrane

PIP3 activation –> PDK1 and Akt (serine threonine kinases) recruited to the membrane via their PH domains causing a conformational change in Akt

Conformational change causes p85 subunit to no longer inhibit p110 on Akt

PDK1 phosphorylates Akt and activates it

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
22
Q

PI3K pathway 2

A

p85 subunit on PI3K has 2 SH2 domains which bind to two neighboring phosphorylated tyrosines –> changes conformation of enzyme –> no longer inhibits p110 –> PI3K phosphorylates at position 3 of PI on the membrane

[PI3,4,5,P3] goes up and this binds to proteins with specific PH domains aka Akt

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
23
Q

Activation of Akt

A

Akt=PKB

PH domain is structured so that it masks the kinase activity on Akt

Once Akt binds to [PI3,4,5,P3] on the membrane, it unfolds and the kinase portion of the enzyme is free

Binding of Akt to PM and phosphorylation of the kinase and hydrophobic tail leads to Akt activation

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
24
Q

Function of Akt

A

Phosphorylates and inhibits multiple substrates like BAD (apoptotic)

Phosphorylates multiple targets related to glucose metabolism and energy homeostasis

25
Q

Akt in parallel with ERK pathway

A

Akt phosphorylates and inhibits TSC2 together with TSC1 which is a GAP for Rheb –> amount of GTPRheb increases since no longer being exchanged out

GTP/Rheb activates serine threonine protein kinase mTORC1 –> increase in protein biosynthesis and cell growth

26
Q

mTORC1

A

Upregulates protein translation

27
Q

TSC

A

Tubular Sclerosis Complex

  • disease from somatic mutations in TSC1 or TSC2
  • formation of benign tumor (size of the cells in the tumor are super large b/c
28
Q

How does the PI3K pathway affect MAP kinase pathway?

A

MAP pathway stays the same…unaffected

29
Q

PLCγ

A

2 SH2 domains and a PH domain that helps to recruit it to the plasma membrane

30
Q

PLCγ Pathway

A

Once at PM + phosphorylation at its receptor, hydrolyzes PIP2 (cleaves it) and produces IP3 and DAG

31
Q

IP3

A

Inositol triphosphate
Very soluble
Binds to specific receptors in ER and releases Ca2+ in the cytosol

32
Q

DAG

A

Diacyl Glycerol

Stays at PM and activates PKC’s

33
Q

Erb B fam

A

Erb B receptor family
These receptors can either homo or heterodimerize after binding to multiple ligands

Erb B expressed in breast, colorectal, and gastric cancers
*dimerization can lead to constant activation of the mutant receptor in absence of the ligand

34
Q

Monoclonal antibodies

A

THERAPY

mABs at an extracellular portion of a mutant receptor can compete with ligands from binding to receptor and deactivate it

35
Q

Cancer therapy

A

specific inhibitors of the kinase domain

36
Q

GPCR

A

G protein coupled receptors are largest family of receptors with enormous diversity of ligands

Can bind to neurotransmitters, odorants, taste ligands, even light

All have 7 transmembrane (7TM) proteins with N-terminus located outside the cell and the C-terminus inside the cell

37
Q

Ligand binding for GPCR

A

Hydrophilic ligands bind to the N terminus or extra cellular loops

Hydrophobic ligands diffuse into the transmembrane and bind to the core of the receptor

38
Q

Trimeric G proteins

A

Therese proteins are anchored to the PM by hydrophobic links
alpha- has a Ras like domain and is a GTPase
beta/gamma

39
Q

GTPase activity of alpha G protein

A

can dissociate from beta/gamma

GDP form: bound to beta/gamma
GTP form: dissociates from beta/gamma
even when dissociated, both units stay on the PM thru hydrophobic links (fatty acid?)

40
Q

Interaction between GPCR and G protein

A

Ligand binding changes conformation of 7-membrane
GPCR….works as GEF and facilitates the exchange of GDP for GTP at the alpha subunit –> activation of alpha

Dissociation of alpha from beta/gamma

Both complexes go their downstream targets and activate different pathways

Eventually, alpha subunit hydrolyzes GTP molecule with the help of a RGS protein

alpha/beta/gamma

41
Q

Downstream targets for beta/gamma

A

-activates PI3K 1B (same pathway as PI3K 1A)

42
Q

Downstream targets for alpha subunit

A

αs: stimulation of adenylyl cyclase (AC)
αi: inhibition of adenylyl cyclase (AC)
αq: phospholipase activity control
α12: downstream activity not known

AC makes cAMP from ATP

PDE’s- phosphodiesterases

43
Q

AC properties

A

AC is localized at the PM

-12 transmembrane domain and 2 catalytic domains

44
Q

PDE

A

phosphodiesterases

3’5’ cAMP cleaves to 5’ AMP which has no signaling significance

can inhibit PDE thru an increase in [cAMP]

45
Q

cAMP

A

10^-7 normal concentration in the cell

decrease in concentration suppresses adenylyl cyclase/ activates PDE

46
Q

PKA

A

cAMP is mediated by tetramer PKA
Also called cAMP dependent protein kinase

Has 2 regulatory subunits and 2 catalytic subunits

In absence of cAMP, the regulatory subunits block the enzymatic activity of the catalytic subunits

Binding of cAMP (cooperatively) to the regulatory subunits causes their dissociation from the catalytic subunits, allowing catalytic subunits to phosphorylate downstream substrates

47
Q

PKA substrates

A

1) Phosphorylase kinase

2) Glycogen synthase regulates transcription

48
Q

PLCβ and Ca++ signaling

A

Activation of PLCβ by an alpha subunit (alpha q) causes hydrolysis of PI4,5,P2 into IP3 and DAG

IP3 migrates to ER where lots of Ca++ is held

IP3 opens Ca++ channels in the ER and the Ca++ rushes into the cytosol where its concentration increases

To terminate signaling, an ATPase pumps Ca++ back into the ER or outside the cell

49
Q

Calcium Calmodulin dependent kinase II

A

4 Ca++ binds to specific sensor calmodulin –> activation of Ca++/calmodulin dependent protein kinase –> self phosphorylation –> locked in active conformation

*even if [Ca] goes down this enzyme stays active until it is dephosphorylated

50
Q

Calmodulin

A

can bind up to 4 Ca++

binding causes conformational changes

51
Q

PKA and PKC for regulation of GPCR’s

A

Can phosphorylate the 3rd intracellular loop and the C terminus of GPCR

52
Q

GRK for regulation of GPCR’s

A

g protein couple receptor kinase

Ligand bound GPCRs can be phosphorylated on the C terminus by GRKs
Phosphorylated receptors interact with arrestins which interfere with binding to G proteins and recruit clathrin and promote internalization of GPCRs

53
Q

Vision

A

Outer segment of rods have membranes enriched in rhodopsin (receptor) bound to 11-cis retinal

Exposure to light –> all-trans retinal –> conformation change in rhodopsin –> exchange of GDP to GTP in alpha subunit of transducin

Free alpha subunit (alpha t) activates cGMP PDE and levels of cGMP go down

cGMP gated cation channels close causing hyperpolarization –> inhibition of synaptic signaling

synaptic signaling characterized by the dark and shut off by the light

54
Q

Color Vision

A

Blue opsin: Chromosome 7
Red/green opsin: X chromosome
^recombine unequally –> explains why males more likely to be color bind

55
Q

Smell

A

thousands of different olfactory GPCRs are expressed in neurons localized in the lining of the nose

GPCR’s coupled to g protein Golf –> subunit dissociates —-> activates adenylyl cyclase –> cAMP gated Na channels open with [cAMP] increase–> depolarization of the cell –> electrical signal is propagated into the brain

56
Q

Taste- 5 different types

A

sour, salty, bitter, sweet, umami

All taste receptors are coupled to the specific G protein called gustducin that activates PLCβ

57
Q

Salty and Sour

A

Salt and sour do not have receptors –> mediated by H+ and Na+ ion channels

58
Q

Sweet and Umami

A

Mediated by 3 GPCR’s that heterodimerize into different combinations

T1R1/T1R3- umami
T1R2/T1R3- sweet

receptors are heterogenous –> different people have different taste thresholds

59
Q

Bitter

A

GPCR T2R family

MoMF (25 decks)

Brainscape helps you reach your goals faster, through stronger study habits.
© 2024 Bold Learning Solutions. Terms and Conditions