Exam 1 cell signalling

Question 1

Pertussis toxin

Answer 1

• toxin is endocytosed and ribosylates the αi subunit (inhibitory subunit) resulting in the protein being locked in the GDP bound state, resulting in increased cAMP. This causes pertussis aka whooping cough.

Question 2

Cholera toxin

Answer 2

• toxin is endocytose into the cell and ADP ribosylates the αs (stimulatory) subunit; inactivates the GTPase activity of the α rendering it permanently active and causing an increase in cAMP. This continuously activates the cystic fibrosis channel (CFTR) causing a big entry of chloride ions and water that follows, causing extreme water loss and dehydration

Question 3

glucagon

Answer 3

binding of glucagon to the receptor allows the α to activate adenylyl cyclase, creating cAMP which adenylyl protein kinase A, which phosphorylates phosphorylase kinase, which phosphorylates glycogen phosphorylase, which phosphorylates glycogen to stimulate glucose release

Question 4

Norepinephrine

Answer 4

binds to a GPCR and activates the G αq subunit (αs/I inhabit and stimulate adenylyl cyclase). Causes phospholipase C to break down PIP2 converting it to IP3 and DAG. DAG activated protein kinase C and IP3 causes Ca ion release from the ER and causing smooth muscle contraction . Vasopressin causes contraction of vascular smooth muscles through this pathway as well

Question 5

Gai

Answer 5

inhibitory; Target-adenylyl cyclase; Use/receptor- Chemokines, a2 adrenoreceptors; Effect- Smooth muscle contraction

Question 6

Gat

Answer 6

activating; Target- Phosphodiesterase; Use/receptor- Rhodopsin; Effect- Vision

Question 7

Gagust

Answer 7

activating; Target- Phosphodiesterase; Use/receptor- Taste receptors; Effect- Taste

Question 8

Gas

Answer 8

activating; Target- Adenylyl cyclase; Use/receptor- adrenoreceptors; Effect- h heart rate, smc relaxation

Question 9

Gaolf

Answer 9

activating; Target- Adenylyl cyclase; Use/receptor- Olfactory receptors; Effect- Smell

Question 10

Gaq

Answer 10

activating; Target- Phospholipase C; Use/receptor- a1 adrenoreceptors; Effect- Smc contraction

Question 11

Ga12/13

Answer 11

activating; Target- Rho (small G protein); Effect- Smc contraction, cytoskeletal function

Question 12

insulin

Answer 12

insulin binding causes autophosphorylation leading to activation of PI3 kinase, leading to formation of PIP3 from PIP2 which activates protein kinase B (aka Akt) which activates glycogen synthase and causes insertion of GLUT4 transporters in the membrane to import glucose.

Question 13

Receptor Tyrosine Kinases

Answer 13

Humans have 58 receptors, specific for hormones, growth factors, etc. Has an N terminal ligand binding domain and a C terminal cytosolic domain with tyrosine kinase activity. Ligand binding leads to cytosolic auto-phsphorylation of the Tyr residues. These are then recognized by SH2 recognition domain proteins which serve as binding sites for downstream signaling molecules

Question 14

Cytokine Receptors

Answer 14

Need cytosolic protein kinases to propagate signal (no kinase activity itself; must harness another kinase to have effect); pathway of cytokines as well as some growth hormones and EPO. Similar to RTKs but have no kinase activity. Ligand binding leads to dimerization and recruits JAK proteins which phosphorylate STAT protein to effect gene transcription

Question 15

Steroid receptors

Answer 15

All act as transcription factors regulating a target gene include glucocorticoid receptors, mineralocorticoid receptors, progesterone receptor, androgen receptor, estrogen receptor, thyroid hormone receptor, vitamin D receptor, and retinoid acid receptor* Structure: 3 domains- conserved hormone binding domain at the C-terminus; a DNA binding domain (zinc finger), and a non-conserved hyper variable region
* Unbound hormone receptors are bound to heat shock proteins (Hsp) or else they are degraded. Binding of hormone results in loss of Hip followed by dimerization and modulation of transcription

Question 16

heat shock proteins (Hsp)

Answer 16

Unbound hormone receptors are bound to heat shock proteins (Hsp) or else they are degraded. Binding of hormone results in loss of Hip followed by dimerization and modulation of transcription. Thyroid hormone, retinoid acid, and vitamin D receptors are not bound to HSPs like the other hormones, they are bound to hormone response elements (HRE) on the 5’ flanking reign of target genes, but inactive until bound to their hormone ligand. There are only 3 HRE classes, but 8 steroid classes, so specificity is achieved through cell specific expression of receptors, formation of heterodimers (e.g. formation of a dimer between a thyroid hormone receptor and a retinoid acid receptor), and other regulatory elements (coactivators)