Enzyme-linked receptors Flashcards
How does ANP activateit’s receptor?
ANP causes Guanylyl Cyclase to dimerize
What does the binding of ANP and dimerization of guanylyl cyclase activate?
GTp -> cGMP
What does cGMP activate?
Protein kinase G
What is the function of protein kinase G?
Phosphorylates & activates proteins to mediate hormone function
How does ANP concentration affect angiotensin?
ANP inhibits angiotensin and aldosterone
Where is ANP released from?
Atrium
How does ANP (ANF) decrease blood volume?
Inhibits Angiotensin & aldosterone to prevent Na+ and water retnetion
Vasodilation
What receptor is capable of phosphorylating itself?
Tyrosine kinase
Name an example of a ligand that binds to a tyrosine kinase receptor
Insulin Fibroblast growth factor Vascular endothelial growth factor Nerve growth factor Epithelial growth factor Platelet derived growth factor
What are the 2 pathways that tyrosine kinase receptors use for phosphorylation?
Insulin Receptor Substrate 1 pathway
MAPK pathway
Describe the IRS-1 pathway
Activated tyrosine kinase receptor associates with IRS-1 and activates phospho-inositol-3-kinase (PI3K)
PI3K mediates vesicles that contain GLUT4
Describe the MAPK pathway
Son of Sevenless adapter protein associates with tyrosine kinase
RAS-GTP activates MAP-kinase pathway
MAPKKK
MAPKK
MAPK
Phosphorylated MAPK translocates to nucleus and activates jun, fos, myc transcription which activate GLUT4
What is RAS?
Protein with intrinsic GTPase used to relay signals to nucleus
What is the active form of RAS?
RAS-GTP
How does a RAS mutation cause cancer? Why is it called the proto-oncogene
RAS that lacks GTPase activity cannot turn itself off and continues signaling for cell proliferation
What is the purpose of the GLUT2 receptor?
Glucose binds to GLUT2 to signal the release of insulin from Beta cells
What is the difference between Insulin deficiency and insulin resistance?
Deficiency has defective Beta cells
Resistant has defective GLUT4. More insulin than normal is needed to activate GLUT4 receptors
What is hyperlipemia and why is it a symptom of diabetes?
Excess fat in the blood
Caused by excess mobilization of fatty acid
What does the excessive mobilization of fatty acids result it?
Ketosis
Sweet breath caused by acetone
What is the purpose of primary response gene bcl2?
Ensure that RBCs survive in the bone marrow long enough to mature
What is JAK2?
An auto-phosphorylating tyrosine kinase receptor
What are the 2 pathways for Erythropoietin receptors?
JAK2/STAT
JAK2/MAPK
Describe the JAK2/STAT5 pathway
Binding of EPO dimerizes receptor
Non-receptor tyrosine kinase binds to dimerized receptor (JAK2)
JAK2 phosphorylates STAT5
STAT5 translocates to the nucleus to begin transcription of bcl2
Describe the JAK2/MAPK pathway
EPO dimerizes receptor
Non-receptor tyrosine kinase JAK2 binds to receptor
SOS binds to JAK2
SOS produces RAS-GTP and activates MAPKKK
MAPKK
MAPK
MAPK translocates to nucleus and acitvates myc, fos, jun
Name a secondary gene primary transcription factors activate transcription for
Cyclin D
What organ produces erythropoietin?
Kidney
What stimulates production of EPO?
Reduction in pO2 (erythrocyte count low or high altitude)
What is the function of EPO?
Increase erythrocyte count by stimulating proliferation in bone marrow
What is the purpose of recombinant human EPO? (rhEPO)
Stimulates red blood cell development
What are side effects of rhEPO?
Increased blood viscosity
Increased chance of embolism
Long term use of rhEPO will shut down natural EPO production