Signal Transduction

Question 1

4 major pathways of cell signaling

Answer 1

1. cell to cell contact/contact dependent
2. hormones/endocrine
3. paracrine/peptides
4. neuronal/small-molecule diffusion

Question 2

cell-cell contact:

ex:

Answer 2

physical contact between 2 cells activates the pathway

e.g: notch signling, where Notch ligand on a “tip” cell contacts Notch receptor on a “stalk” cell, signaling the release of the cytoplasmic domain of notch (NICD), which goes to nucleus and activates gene expression by binding TF CSL (a repressor of thousands of genes), thereby releiving the inhibition of CSL and a a result, activating many genes. stalk cell forms a blood vessel lumnen

Question 3

peptide/paracrine signaling

Answer 3

• peptide signaling by neighbors bind to cell receptors and induce cell response on cytoplasmic side of memb.
• local effects

Question 4

neuronal signaling

Answer 4

signaling by neighbors, local effects, “anatomically” directed synapse, small molecule diffuses into cell.

Question 5

hormone signaling

Answer 5

• steroid molecules released at a distance
• hydrophobic nature allows them to travel freely thru the cell membrane, bind to intracellular receptors, and therefore enter nucleus and alter gene expression

Question 6

NO as a cell signaling molecule:

Answer 6

1. AcCh from neurons binds to endothelial cell receptor, inducing production of nitric oxide in
2. NO from endothelial cells diffuses to neighboring smooth muscle cells, where it binds to target proteins and relaxes the cell.

Question 7

G-Protein-Coupled Receptors

Answer 7

• 7 TM spanning receptors, 3 subunits. alpha and gamma subunits are attached next to the receptor by lipid linkages.
• When a ligand binds GPCR (a GEF), GTP binds to its alpha subunit. alpha-GTP dissociates from beta and gamma subunits.
• alpha subunit and beta,gamma subunit can signal to downstream players.
• beta gamma can activate K channels
• GTP-A binds adenylyl cyclase, phospholipase C, and other target proteins at membrane and activates them.
• when alpha subunit hydrolyzs GTP-A to GDP-A, it recombines with beta and gamma subunits. G-protein is dormant until re-activated by a GPCR.

Question 8

cAMP as 2nd messenger

Answer 8

1. alpha subunit activates adenlyl cyclase which converts ATP to cAMP
2. cAMP binds to protein kinase A
3. PKA moves into the nucleus and phosphorylates TFs

cAMP is short-lived due to phosphodiesterase

Question 9

IP3 as a 2nd messenger:

Answer 9

1. GTP-A activates phospholipase C, which cleaves PIP3 into IP3 and diacylglycerol (DAG).
2. IP3 works to open Ca++ channels and increase cytoplasmic Ca++

Question 10

Tyrosine Kinase Receptors

Answer 10

• ligands are dimers that bind and dimerize receptors.
• cross-phosphorylation: each chain becomes an active kinase and phosphorylates each other. Results in activation of adaptor proteins bound to dimer, which activate Ras, a GTPase
• Ras GTPase acivates MAP kinase –> MAPKK–> MAPKKK–> many genes and proliferation
• Ras is an oncogene

Question 11

Split Tyrosine Kinase Receptors

Answer 11

• receptors are not enzymes and cannot activate phosphorylation, so they recruite a tyrosine kinase like JAK. JAK binds receptors and phosphorylates other sites on the receptor which bind to STATs.
• STATs are phosphorylated, dimerize, move into the nucleus, and activate gene expression

Question 12

Serine Threonine Kinase Receptors

Answer 12

• one receptor phosphorylates its partner receptors and this cross phosphorylates leading to binding of SMADS transcription factors.
• SMADS are phosphorylated and go to nucleus to regulate the genome
  *

Question 13

PIP3

Answer 13

a survival signal that activates AKT, PDK1 (kinases) which affect cell survival mechanisms called mTOR

Question 14

nuclear receptors are typically

Answer 14

TFs that bind hydrophobic ligaments

Question 16

interleukins are associated w

Answer 16

STAT dimerization