Single Transmembrane Receptor Signaling

Question 1

Cytokine Receptors and the JAK/STAT Pathway:
a ligand binds to its receptor leading to receptor [1]
Cytokine receptors utilize an [2] kinase unlike RTKs/TGF-beta
This kinase is called [3] which self phosphorylates the [4] domain and phosphorylates tyrosine residues on the cytosolic side of the receptor tail.
This attracts a protein called [5] with a [6] domain.
Phosphorylation, dimerization, and transcription factor function ensues.

Answer 1

[1] dimerization
[2] extrinsic
[3] JAK
[4] lip tyrosine
[5] STAT
[6] SH2

Question 2

Examples of [1] Signaling:

1. Interferon Response
2. Prolactin Signaling
3. Hematopoietic RBC Differentiation

Answer 2

[1] Cytokine

Question 3

Hypoxia, Epo, and Cytokine Signaling:
Hypoxia leads to [1] synthesis in the kidneys. This dimerizes as a transcription factor to increase [2] synthesis. Secreted and binds to [3] in the bone marrow for RBC production. One RBC levels restored, [4] leads to [1] degradation.

Answer 3

[1] HIF-1alpha
[2] Epo (erythropoietin)
[3] EpoR
[4] VHL

Question 4

23 year old woman presents complaining of diffuse pain, fatigue, and leg numbness. Unsteady when standing, mildly spastic gait, decreased leg strength, blurry eyesight, and hyperreactive reflexes.
The MRI of her brain will most likely revel [1].

Answer 4

[1] Multiple Sclerosis Plaques

Question 5

MS: Autoimmune Disease Degrades [1]

genetic, viral infection, or smoking increases risk

Answer 5

[1] Myelin

Question 6

MS Treatment through [1] Therapy
suppress [2] cytokines and/or express [3] cytokines.

Really, we are looking to utilize [4] signaling.

Answer 6

[1] Steroids and Interferon (Anti-Inflammatory)
[2] pro-inflammatory
[3] anti-inflammatory
[4] IFN-beta (JAK/STAT)

Question 7

RTKs utilize [1] kinases that are encoded into the receptor itself (not associated protein)

Answer 7

[1] intrinsic

Question 8

RTKs activate the [1] GTP-binding protein on the cytosolic side.
[2] is the GEF nucleotide exchange factor that docks between the receptor and this protein and adds a GTP. This sis attached to the actual receptor via [3] that has a SH2 domain.

Answer 8

[1] Ras MAP Kinase
[2] Sos
[3] GRB2

Question 9

The Ras-MAPK Pathway

Ras activates [1] that activates [2] that activates [3].
Allows for amplification along the way.

Answer 9

[1] Raf
[2] MEK
[3] ERK
– MAPK that phosphorylates transcription factors

Question 10

Examples of [1] Signaling:

1. Epidermal Growth Factor Receptor (EGFR)
   - deregulated in cancer
2. Vascular Endothelial Growth Factor Receptor (VEGFR)
   - angiogenesis
3. Insulin Receptor
   - ineffective in Type 2

Answer 10

[1] RTK (Receptor Tyrosine Kinase)

Question 11

Epidermal Growth Factor Signaling:
EGF binds [1] –> Ras-MAPK and growth
a mutant [1] will stimulate growth in the absence of the EGF ligand (cancer)
[2] amplification in breast cancer
– monoclonal antibodies (drug = [3]) effective in treating these breast cancers

Answer 11

[1] HER (dimerizes when ligand binds)
[2] HER2
[3] Herceptin

Question 12

TGFbeta/Smad Signaling Pathway:
[1] is the transcription factor that gets phosphorylated
The [2] component has the active intrinsic kinase that phosphorylates the TF.
The [3] component has an intrinsic kinase that activates [2].
The [4] component can be ligand-binding.

Answer 12

[1] Smad
[2] R1
[3] R2
[4] R3

Question 13

Anti-Cancer Properties of TGFbeta Signaling:
1. Formation of more stable tissue. Secreted ECM proteins by fibroblasts AND [1] inhibit serum proteases that degrade much matrix proteins
– [1] transcribed by TGFbeta signaling
2. Inhibit cell cycle and growth
indices [2], a cell cycle inhibitor

Answer 13

[1] PAI1

[2] CDKI p15

Question 14

Inactivating TGFbeta or [1] mutations in many cancers, including pancreatic
retinoblastoma, colon, and gastric cancers often unresponsive to TGFbeta signals —> R1 or R2 loss

Answer 14

[1] Smad

– induce p15 cell cycle inhibitor // Smad4 deletion