Lecture 15 - Signal Processing Pathways II

Question 1

Effector proteins can be

Answer 1

Metabolic enzymes
Gene regulatory proteins
Cytoskeletal proteins

Question 2

mTOR signalling pathway

Answer 2

Mammalian Target of Rapamycin

pathway inhibited by rapamycin

Question 3

Rapamycin causes a

Answer 3

Decrease in cellular growth

Eventually causes apoptosis

Question 4

mTOR is a

Answer 4

Cytoplasmic Kinase

Phosphorylates Ser/Thr residues

Question 5

mTOR is central to

Answer 5

Control of cellular growth and proliferation

Linked to cancer cell growth

Question 6

mTOR is regulated by

Answer 6

Growth factors, RTKs, Insulin, Nutrients (a.a. and glucose), cellular energy levels, stress

Question 7

mTOR complexes into

Answer 7

mTORC1 and mTORC2

Question 8

The mTOR cascade is activated by

Answer 8

RHEB

Ras Homolog Enriched in Brain

Question 9

RHEB is

Answer 9

A Ras family small GTPase

Question 10

When RHEB is bound to GTP it

Answer 10

Activates mTOR (then cells can grow)

Question 11

The mTOR pathway is regulated by

Answer 11

TSC1 and TSC2

Question 12

TSCs

Answer 12

Tuberous Sclerosis Complex

Question 13

TSC1 and TSC2

Answer 13

Inhibit the mTOR pathway (growth suppressors)

Question 14

TSC2 inactivates

Answer 14

RHEB by GTP hydrolysis - TSC2 is a GAP (GTPase activating protein)

Question 15

Activated AKT (kinase) phosphorylates and inhibits

Answer 15

TSC2

Question 16

AKT/PKB

Answer 16

A serine/threonine-specific protein kinase that plays a key role in multiple cellular processes such as glucose metabolism, apoptosis, cell proliferation, transcription and cell migration

Question 17

Starvation results in

Answer 17

Autophagy

Question 18

Aktivation of mTOR results in

Answer 18

Phosphorylation of downstream targets

Question 19

mTORC1

Answer 19

Promotes protein synthesis
Promotes ribosome production
Inhibits protein degradation

Question 20

mTORC2

Answer 20

Changes actin cytoskeleton and cell shape

Question 21

mTOR activates S6 kinase that

Answer 21

Phosphorylates ribosomal protein S6

Increases translation of ribosomal components

Question 22

elF4E

Answer 22

Translation initiation factor

Indirectly activated by mTOR by inhibiting an inhibitor of elF4E

Question 23

mTOR is a central

Answer 23

Modulator of proliferative signal transduction
Integrates external and internal signals
Co ordinates cellular growth and replication

Question 24

mTOR is an ideal therapeutic target against

Answer 24

Cancer

Multiple components of pathways that signal through mTOR as dysregulated in cancer

Question 25

Clinical inhibitors of mTOR

Answer 25

Rapamycin (bacterial toxin) Immunosuppressants Anti cancer drugs

Question 26

Tuberous Sclerosis

Answer 26

Multi system genetic disease Mutations in TSC1 or 2 (hamartin and tuberin) Cause non malignant tumours in the brain and other vital organs Loss of control of cell growth and division developmental delay, skin abnormalities, lung and kidney disease

Question 27

Mating factors cause

Answer 27

Polarisation of yeast cells | "Schmooing"

Question 28

Polarisation of yeast cells | "Schmooing" Steps

Answer 28

1. Mating factor - activates G protein 2. Activates Cdc42 (Rho family) 3. Rho - formin - actin cable formation 4. Polarised exocytosis and schmooing

Question 29

Cdc 42 also activates WASP and ARP complex to

Answer 29

Local actin nucleation at the site of mating factor binding, actin filament polymerisation, actin cable formation (tip growth)

Question 30

The insulin signalling pathway is a

Answer 30

RTK | Present on the surface of insulin responsive cells (Muscle, Liver, Fat)

Question 31

RTK have

Answer 31

``` 2 subunits held together by disulfide bonds alpha units (extracellular) bind insulin beta units (transmembrane and intracellular) ```

Question 32

Binding of insulin to the RTK causes

Answer 32

Intracellular domains to come together, allowing cross phsophorylation Leads to docking and phosphorylation of other proteins

Question 33

Insulin in liver cells results in

Answer 33

Increased glycogen synthesis A.a metabolism Growth Glucose translation

Question 34

Insulin in muscle cells results in

Answer 34

Increased growth Myoblast fusion Glucose translocation

Question 35

Insulin in fat cells results in

Answer 35

Adipogenesis | Glucose translocation

Question 36

In less differentiated cells prolonged glucose activation

Answer 36

Leads to long term activation of gene loci - results in cellular differentiation