G protein coupled receptors Lecture 3

Question 1

Cancer is a disease of genetic alterations. Which genes are altered?

Answer 1

• Oncogenes

- tumor suppressor genes

Question 2

An _____ is a mutated photo-oncogene.

Answer 2

Oncogene

Question 3

How is Palladia a competitive inhibitor of ATP?

Answer 3

Palladia blocks ATP binding to the kinase domain of the KIT RTK

Question 4

Rhodopsin and olfactory receptors are examples of _____ ______ _____ receptors. What does each do?

Answer 4

• G protein Coupled receptors
• Rhodopsin is a light receptor in rod cells in the eye that functions as a visual pigment protein
• Olfactory receptors contribute to your sense of smell

Question 5

How do G protein coupled receptors function?

Answer 5

Ligand binding causes a conformational change in the receptor that causes the G protein alpha subunit to exchange GDP for GTP and dissociate from the beta and gamma subunits. The beta and gamma subunits bind to and activate downstream signaling pathways. Hydrolysis, or loss of ATP, of the alpha subunit causes the subunit to reassociate with the beta and gamma subunits and reassemble the inactive complex.

Question 6

What is reduced rhodopsin function associated with? What is complete loss of rhodopsin function associated with?

Answer 6

Night blindness, and complete loss of rhodopsin function results in complete blindness

Question 7

Mutations in the rhodopsin gene cause a loss of rhodopsin function, which is a cause of canine _____ ______ _____.

Answer 7

-Progressive Retinal Atrophy

Question 8

Describe the cause of progressive retinal atrophy in English Mastiffs.

Answer 8

A missense mutation occurs in the rhodopsin G protein coupled receptor, which results in a single nucleotide change that produces a new 3 letter codon coding for a different amino acid. This reduces the function of the rhodopsin G protein coupled receptor and causes blindness.

Question 9

_____ ____ genes are one of the largest gene families in mammalian genomes. Describe the consequences of this.

Answer 9

• Olfactory receptor
• With over 800 olfactory receptor genes, there is a high degree of polymorphism, or nucleotide variants, in olfactory gene sequences among dog breeds. This is why some dog breeds have a greater sense of smell than others.

Question 10

_____ are a subset of steroid hormones that influence glucose and protein metabolism. Two examples of these are _____ and _____.

Answer 10

• Glucocorticoids

- Cortisol

Question 11

______ is a potent, synthetic steroid hormone that exhibits glucocorticoid-like activity. Describe its properties.

Answer 11

• Predisone

- It is more potent and has a longer half-life compared to natural glucocorticoids

Question 12

Without prednisone or cortisol as a ligand, the glucocorticoid receptor is localized where? What is it bound to?

Answer 12

• Cytoplasm

- Heat shock proteins and a protein called FKBP52

Question 13

Steroid hormones are relatively _____ so they can diffuse through the plasma membrane into the cytoplasm and bind to glucocorticoid receptors. What happens when they bind?

Answer 13

• lipophilic
• When steroid hormones bind to the glucocorticoid receptor, the heat shock protein (HSP) is released. The free glucocorticoid forms a dimer with another glucocorticoid:cortisol complex, and then this dimer moves to the nucleus. In the nucleus, it binds to the glucocorticoid response element (GRE), which activates the transcription of steroid hormone responsive genes