Lecture 17: Cell Signaling pt. 3

receptor tyrosine kinase

most common, largest class of receptor

most common type of growth factor receptor

protein tyrosine kinases

steps of growth factor signaling

1. Signal molecule binding induces dimerization of the receptor

2. Activated receptor tyrosine kinases phosphorylate themselves

3. Triggers assembly of intracellular signaling complex on receptor tails

Ras

small, membrane bound monomeric G protein

how is ras activated?

many receptor tyrosine kinases

inactive Ras

GDP bound

active Ras

GTP bound

MAP kinase

mitogen activated protein kinase

MAP kinase pathway

1. growth factor binding leads to ras activation

2. activates ras recruits raf

3. activates raf turns on MAP kinase pathway

4. phosphorylate ERK

5. ERK turns on genes that promote cell proliferation and inhibits apoptosis

growth factor signaling through MAP kinase pathway

growth factor binding leads to ras activation, which recruits raf and turns on MAP kinase pathway

scaffold protein KSR

organizes MAP kinase signal cascade by functional groups, leading to efficient and specific activation of the pathway

cAMP

cGMP

IP3

opens Ca++ channel, results in rise in intracellular Ca++

Ca++

binds to Calmodulin to activate Myosin Light Chain Kinase (MLCK)

contraction of actin-myosin bundles mechanism

1. Ca++ binds to calmodulin, activating MLCK

2. MLCK phosphorylates myosin light chain, enabling myosin motor domain to move

3. Ca++ interacts w/ troponin to expose myosin binding site on actin

4. result: sliding of actin and myosin filaments relative to each other

TGF-β signaling

1. TGF-β I and II form dimer upon ligand binding

2. type II phosphorylates type I, which phosphorylates smad proteins

3. smad proteins form complex

4. complex enters nucleus and activates gene expression

NF-kB signaling

• receptor recruits adaptor protein that activates IkB kinase (inhibitor)

• phosphorylated IkB is ubiquitylated and degraded

• NFkB enters nucleus and activates target genes for inflammation

Notch signaling

• binding of delta leads to proteolytic cleavage of Notch by γ-secretase

• The intracellular domain Notch enters nucleus to activate gene expression

wnt signaling

• wnt binds to Frizzled and LRP receptor

• recruit dishevelled

• inactivation of destruction complex

• β catenin enters nucleus and binds to TCF to activate gene expression