The M C M 2 - 7 proteins form a six-member ring-shaped complex around DNA. MCM 2, 3, 5 are regulatory, while MCM4,6,7 have helicase activity.

TLS Online TPP Program

#Id: 9642

#Unit 4. Cell Communication and Cell Signaling

In unstimulated cells, 

Raf is phosphorylated by several cytosolic kinases on two sites:

1. Serine/threonine kinase domain 

2. N-terminal autoinhibitory domain

TLS Online TPP Program

#Id: 9643

#Unit 4. Cell Communication and Cell Signaling

Molecular Handcuff 

Phosphorylation of Raf is recognize by protein 14-3-3 dimer, which locks the autoinhibitory domain in a position where it blocks and inhibits the kinase active site

TLS Online TPP Program

#Id: 9644

#Unit 4. Cell Communication and Cell Signaling

TLS Online TPP Program

#Id: 9645

#Unit 4. Cell Communication and Cell Signaling

Active Ras⋅GTP binds to the N-terminal autoinhibitory domain of Raf, altering its conformation and allowing the phosphate attached to this domain to be removed by cytosolic phosphatases, causing loss of 14-3-3 binding.

TLS Online TPP Program

#Id: 9646

#Unit 4. Cell Communication and Cell Signaling

Active Raf phosphorylates MEK on one or two serine residues in its activation loop, activating MEK kinase activity

TLS Online TPP Program

#Id: 9647

#Unit 4. Cell Communication and Cell Signaling

Constitutively active Raf kinase

a glutamic acid substitution for the valine at position 600