Cell Signaling

Question 1

cell-surface receptor

Answer 1

on plasma membrane

small hydrophilic signaling molecues - can’t pass PM

cytoplasmic domain sends signals

Question 2

intracellular receptors

Answer 2

ligand is hydrophobic and bound on a carrier protein - can cross plasma membrane into nucleus

Question 3

Nitric Oxide gas

Answer 3

vasodilator!

nerve –> endothelial cell, rapid diffusion across cell membrane

Nitroglycerin –> NO

NO binds to guanylyl cyclase which turns GMP to cGMP –> rapid relaxation of smooth muscle cell

Phosphodiesterase Type 5- breaks cGMP back to GTP - if inhibited - more cGMP, more vasodilation (viagra)

Question 4

Phosphodiesterase 5

Answer 4

breaks cGMP back to GTP

if inhibited –> vasodilation!

viagra

Question 5

steroid receptor domains

Answer 5

1. ligand binding
2. DNA binding
3. transcription activating

(also inhibitor bind)

if steroid binds –> inhibitor falls off –> can bind DNA

Question 6

antiestrogens

Answer 6

Tamoxifen

like estrogen binds to receptor but binds repressors and turns off transcription

breast cancer –> estrogen –> growth

Question 7

ion channel linked receptors

Answer 7

ligand - change permeability! receptor is an ion channel

Question 8

GPCR

Answer 8

largest family of receptors

pass throguh cell membrane many times

alpha - bound to GTP or GDP - to activate - activate target protein

alpha has intrinsic GTPase activity –> takes off GDP and turns self off

alpha proteins bind diff proteins, bind diff receptors - specificity

Question 9

CCR5

Answer 9

cytokine receptor - HIV uses it to get into cells

some w mutation can’t be infected!

Question 10

Tyrosine Kinsase

Answer 10

phophorylates on OH

Insulin, EGF, PDGF

MOST

Question 11

Serine/threonine kinase

Answer 11

TGF beta

Question 12

cytokine receptor

Answer 12

cytosolic kinase associates w the receptor

Question 13

phosphorylation

Answer 13

phosphate from ATP

negative - changes shape

binding site for other proteins –> recruit proteins to activate

Question 14

TGF

Answer 14

signals via surface serine/threonine kinase receptor

ligand binds –> dimerize –> activate kinase domain by transphosphorylating –> smad 2 or 3 localized and phosphorylated (trnascrotion factor) –> binds to smad 4 –> goes to nuclues and activates transcription of target genes

Question 15

fibrosis

Answer 15

fibrosis - turning genes such as collagen and fibronectin and inhibiting proteases that break down matrix

Question 16

tumor suppressor

Answer 16

turning on genes involved in growth arrest and inhibition of genes that are pure growth

Question 17

RTK signaling

Answer 17

inactive in membrane

signal binds –> dimerize –> phosphorylate tyroside residues by cross phosphorylation (many times - activate kinase so more active) –> recruits proteins with SH2 domains (signalling proteins that bind to phosphorylated tyrosines) –> recruit range of singlal molecules

Question 18

SH2 domain

Answer 18

proteins have diff catalytic activities - which domain it is recruited to

SH2 binding - allows protein to dock on phosphorylated tyroside resides on other proteins - docking only

has bind site for phosphotyroside and for AA side chain - specificity for which Tyr = which signal molecule is recruited

biological outcome is related to the combination of SH2 domain containing proteins recruited

Question 19

PLC gamma

Answer 19

RTK bind ligand - phosphorylate tyrosines –> PLC docks on SH2 domain –> enables kinase to tyrosine phosphorylate PLC and put it’s next to PIP2 hich is it’s substrate (needs to cleave)

Question 20

Jak2 kinase

Answer 20

binding of interferon –> cross links adjacent receptors –> Jaks on receptors cross phosphorylate each other on tyrosines –> activated Jaks phosphorylate the receptors on tyrosines –> activated jaks phosphorylate cytoplasmic tyrosine kinase

Question 21

Ras

Answer 21

first oncogene discovered!

mitations in normal genes result in constitutive activation of proteins encoded by these genes

proto-onco Ras mediates bio processes and activated by receptors - like cell growth and differentiation

EGFR binds –> RTKs phosphorylate each other –> Grb2 docks by SH2 domain –> SH3 domain binds Sos –> acivates Ras which is a transcription factor –> activates MAP kinase pway for growth