Tyrosine Kinase Signalling Pathways Flashcards

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1
Q

What receptors do hydrophilic molecules interact with?

A

Hydrophilic molecules cannot pass through membranes, so have to interact with extracellular receptors.

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2
Q

What receptors do hydrophobic molecules interact with?

A

Hydrophobic molecules can pass through membranes so can interact with intracellular receptors.

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3
Q

What is a transmembrane receptor made up of and what does it do?

A

A cystine rich hydrophobic domain (head) which interacts with the ligand.
A hydrophobic tyrosine kinase domain (tail) that interacts with downstream signalling machinery.

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4
Q

How is information transmitted from the ligand receptor to the effector?

A

Dimerization.
Conformational changes to membrane receptors, which are associated with G proteins.

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5
Q

What is dimerization?

A

Each ligand binds to a receptor.
The receptor brings the ligands together and they activate each other.

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6
Q

What is a Drosophila eye made up of?

A

Each eye is made of 800 ommatidia.

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7
Q

What is in an ommatadia?

A

8 photoreceptors
4 cone cells
2 primary pigment cells
6 secondary pigment cells
3 tertiary pigment cells

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8
Q

What pathway is required for R (photoreceptor) cell recruitment?

A

Ras / Raf / MEK / ERK pathway.

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9
Q

What is Ras?

A

A small GTPase. Controlled by GEFs and GAPs.

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10
Q

What is a GEF?

A

G protein exchange factor.

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11
Q

What is a GAP?

A

GTPase activation protein.

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12
Q

What happens in the first stage of the Ras pathway?

A

PDGF ligand is dimerized.
It has a high affinity for receptors (K alpha)

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13
Q

What is the affinity for K alpha receptors?

A

10^-10 M

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14
Q

What happens in the second stage of the Ras pathway?

A

Trans membrane P-Y residues are phosphorylated in cytositic tail.

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15
Q

What happens in the third stage of the Ras pathway?

A

P-Y residues bind to SH2 domain on GRB2 adaptor protein.

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16
Q

What happens in the fourth stage of the Ras pathway?

A

SH2 binds to SOS protein which is a GEF.

17
Q

What happens in the fifth stage of the Ras pathway?

A

SOS-GEF switches GDP to GTP, which activates Ras.

18
Q

What happens in the sixth stage of the Ras pathway?

A

Ras-GTP is binds to inhibitory domain of MEK. MEK is switched on.

19
Q

What happens in the seventh stage of the Ras pathway?

A

MEK activates ERK.
MEK and ERK are S/T kinases.

20
Q

What happens in the eighth stage of the Ras pathway?

A

ERK translocate to the nucleus and interacts with TIS, triggering gene expression.

21
Q

What signalling pathway is activated in 80% of melanomas?

A

Ras / Raf / MEK / ERK

22
Q

What mutation in the Ras pathway causes melanoma?

A

V600.
In the kinase activation loop.

23
Q

What was / is melanoma treated with.

A

Melanoma was treated with BRAF kinase inhibitors, which works well at first before resistance is developed.
Now, BRAF and MEK inhibitors are used.

24
Q

What is the JAK / STAT signalling pathway?

A

Made of 4 janus kinases
and 7 signal transducer and activator transcriptions

25
Q

What are the 4 janus kinases? (JAK)

A

JAK1
JAK2
JAK3
TYK2

26
Q

What are the 7 signal transducer and activator transcription (STAT)

A

STAT1-4
STAT5a
STAT5b
STAT6

27
Q

What mutation causes myleoproliferatice neoplasms?

A

JAK2 V617F

28
Q

What is a type I inhibitor?

A

Bind to active conformation of the kinase. Aspartate residue facing the ATP binding pocket.

29
Q

What is a type II inhibitor?

A

Bind to the inactive conformation of the kinase. Aspartate residue binds facing away from ATP binding pocket.

30
Q

What is a type III inhibitor?

A

Occupy an allosteric pocket adjacent to ATP binding site.

31
Q

What is a type IV inhibitor?

A

Occupy an allosteric pocket away from ATP binding pocket.