BIOL 310 - Molecular Cell Biology: RTK and MAPK signaling pathways

From Lodish Chapter 16.3-4, 12.6-7

What happens when a ligan binds to an RTK?

RTKs dimerize and activate

What happens once RTKs are dimerized?

phosphorylation of activation loop kinases,, then the phosphorylation of additional tyrosine residues on RTK cytosolic domain

What keeps RTK in the membrane?

Transmembrane alpha helix

What are the major ligands for RTKs?

Growth factors

What do growth factors do?

Regulate major cell processes (like cell cycle and cell differentiation)

What happens if a growth factor is disrupted or disregulated?

Diseases or cancers

What happens after phosphorylation of RTK’s cytosolic domain?

Downstream signaling cascade, eventually reaching Ras

What is Ras?

Protein used in Ras/MAPK pathway

Member of GTPase superfamily

GTP/GDP determines on/off state (Often GTP is the active state)

What is bound to Ras when it is active? What happens when it is active?

GTP, downstream signaling

What is the order of the Ras/MAPK pathway?

Ras-Raf-MEK-MAPK

What is the category of the four proteins in the Ras-Raf-MEK-MAPK pathway?

Kinase

What are the two ways the signal MAPK can get into the nuclueus?

Entire dimeric molecule of MAPK enters through NPC

Active p90RSK (phosphorylated) enters through NPC

What does MAPK do in the nucleus?

Phosphorylates TCF (ternary complex factor)

What does p90RSK do in the nucleus?

Phosphorylates SRF (serum response factor)

What does MAPK activate in the nucleus?

c-fos gene

How are different MAP pathways separated?

Scaffold proteins hold stuff in place

What is R7 in Drosophila? What does it do?

1 photoreceptor part of 8-part compound eyes, allow flies to see in UV spectrum

What are the signaling molecules involved in promoting an R7 precursor to an R7 neuron? Where are they located?

R8 - Boss (Bride of sevenless)

R7 precursor - Sev (sevenless)

What is a proto-oncogene?

Gene that works normally but becomes cancerous

What is a ligand-independent receptor oncoprotein?

Receptor proteins are always dimerized

How does HER2 become cancerous (NEU oncoprotein)?

Valine in trans-membrane alpha helix exchanged for a glutamine, causing dimerization

How does EGF receptor become cancerous (ErbB oncoprotein)?

Protein tyrosine kinase on receptor is constitutively (inherently) active