Single Pass Transmembrane Receptor Signaling Flashcards Preview

Biochem > Single Pass Transmembrane Receptor Signaling > Flashcards

Flashcards in Single Pass Transmembrane Receptor Signaling Deck (29)
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1
Q

Which single pass receptors have their kinase as part of their intracellular domain?

A

Intrinsic kinase, RTKs, and TGFB receptors

2
Q

Which single pass membrane receptors have the kinase as a separate protein?

A

Extrinsic kinase, cytokine receptors

3
Q

JAK/STAT is an example of what kind of receptor?

A

Cytokine receptor

4
Q

JAK/STAT pathway

A
  1. Cytokine receptor binds ligand
  2. Receptor dimerizes, bringing together the JAK kinases in the intracellular domain
  3. The JAKs autotransphosphorylate on tyrosines of their Lip domain
  4. Activated JAK phosphorylates tyrosines on the receptor’s intracellular domain
  5. Phosphotyrosines recruit STAT via its SH2 docking site
  6. JAK phosphorylates STAT
  7. STAT dimerizes through its own SH2 domains and phosphotyrosine residues, then goes to the nucleus to mediate transcriptional gene expression
5
Q

Where is erythropoitetin produced? Where does it work?

A

Produced in the kidneys; stimulates RBC prodouction in bone marrow

6
Q

In cytokine receptors, the phosphotyrosine residues on the intracellular domain of the receptor serve to

A

dock a scaffold of proteins that have SH2, SH3, or PTB domains; these proteins allow for further phosphorylation or recruits additional signaling proteins in the cascade

7
Q

JAK

A

Extrinsic protein kinase that is associated with the intracellular domain of a cytokine receptor, but is a separate protein

8
Q

Which signaling pathway is involved in responding to interferons? What are interferons?

A

JAK/STAT

Interferons bind to cells to stimulate an antiviral response.

9
Q

Which signaling pathway is associated with lactation?

A

JAK/STAT generates prolactin signals to alter the metabolism of mammary cells for milk produciton

10
Q

Erythropoietin (Epo) - what does it do and and what kind of receptor does it use?

A

Stimulates RBC production.

Epo receptor is a cytokine receptor that mediates proliferation & differentiation of the erythroid progenitor cell into mature RBCs.

11
Q

Multiple sclerosis

A

Autoimmune disease in which T cells and monocytes degrade the myelin sheath

  • remission & recurrence
  • fatigue, trouble walking & balance, muscle weakness, blurred vision
  • can result from viral infections (Epstein-Barr, Herpes virus-6)
12
Q

Treatment fo rMS

A

Steroids reduce inflammation

Interferons signal the cytokine JAK/STAT pathway to produce anti-inflammatory signals while inhibiting pro-inflammatory signals

13
Q

Monomeric G proteins play an integral role in what kind of receptors?

A

RTKs

14
Q

GEF vs GAP

A

GEF turns on the monomeric G-protein by exchanging the GDP for GTP

15
Q

While RTKs have intrinsic tyrosine kinase domains and cytokine receptors have extrinsic ones, how are the receptors similar?

A

Both exist as a monomer, whose ligation promotes dimerization > brings together the kinase domains for autophosphorylation of the Lip domain and activation of the kinase > kinase phosphorylates intracellular Tyrs > phosphotyrosines serve as dockign sites for protein-protein interacitons with other intracellular signaling molecules > signal amplification > altered gene expression and cellular fxn

16
Q

The Ras-MAP kinase pathway uses what kind of receptor?

A

RTK

17
Q

Describe the Ras-MAP kinase pathway, starting from the receptor phosphotyrosines

A
  1. Receptor phosphotyrosines dock GRB2 and SOS thorugh SH2 & SH3
  2. SOS is a GEF for Ras, so it activates it
  3. Activated Ras-GTP can now activate the MAPK pathway (Ras-Raf-Mek-Erk)
  4. Erk/MAP kinase dimerizes and goes to the nucleus to phosphorylate and activate tf’s
18
Q

How can Ras mutations cause cancer?

A

If Ras can’t hydrolyze GTP (such as in RASGly12), it’s permanently active and will stimulate continual MAPK activity –> cancer growth

19
Q

What type of receptor includes many growth factor receptors such as EGFR, PDGFR,FGFR, VEGFR, RET

A

RTKS

20
Q

The insulin receptor is what type of receptor?

A

RTKs involved in metbaolism

21
Q

type 2 diabetes can result form a defect in what type of receptor?

A

RTK - the insulin receptor is an RTK involved in glucose and lipid metabolism pathways

22
Q

Why are HER2 monoclonal antibodies effective in treating HER2 positive breast cancers?

A

HER2 is an RTK that promotes growth.

23
Q

What is TGFB? What does it result in?

A

The ligand of the Smad signaling pathway, which leads to secretion of ECM proteins from epithelial and fibroblast cells

24
Q
A
25
Q

TGFB/Smad Signalign pathway

A
  1. TGFB (ligand) binds its already-phosphorylated RII receptor
  2. RII receptor phosphorylates & activates RI on its intracellular domain
  3. RI phosphorylates SMAD transcription factors
  4. Smad3 unmasks a nuclear localization sequence
  5. Two Smad3’s and a Smad4 combine into a trimer through phosphorylation interactions and enter the nucleus via importin to cause changes in gene expression
26
Q

What does TGFB signaling do?

A
  • Secretion of ECM proteins from epithelial and fibroblast cells
  • Secretion of serum protease inhibitors (which degrade ECM proteins)
  • Signals for Cycling-Dependent Kinase Inhibitor (CDKI) p15, which causes cell cycle arrest
27
Q

What signaling pathway is anti-growth? How?

A

TGFB/Smad

  • Secretion of PAI1 suppresses migraiton into tissues by forming a new tissue
  • CDKI p15 causes cell cycle arrest
28
Q

Smad4 is assocaited with what type of cancer?

A

Pancreatic cancer ; originally, Smad4 was called Deletion in Pancreatic Cancer (DPC

29
Q

Reitnoblastoma, colon, and gastric cancers have what problem with the TGFB pathway?

A

RI or RII receptosr are deleted