TLS Online TPP Program

#Id: 9621

#Unit 4. Cell Communication and Cell Signaling

Kinase domains typically contain two regions:

N and C lobes

TLS Online TPP Program

#Id: 9622

#Unit 4. Cell Communication and Cell Signaling

Monomeric state of the EGF receptor,

activation loop is situated in the active site of the kinase near the interface of the N and C lobes, blocking the site’s activity; in this way the kinase is maintained in the inactive or “off” state

TLS Online TPP Program

#Id: 9623

#Unit 4. Cell Communication and Cell Signaling

Asymmetric kinase dimer 

Receptor dimerization brings the kinase domains of the two subunits close together, so that the C lobe of one kinase domain binds to the N lobe of the other kinase domain

TLS Online TPP Program

#Id: 9624

#Unit 4. Cell Communication and Cell Signaling

Two Mechanisms Down-Regulate Signaling from RTKs

1. Phosphotyrosine phosphatases

2. Receptor-mediated endocytosis followed by degradation in lysosomes

TLS Online TPP Program

#Id: 9625

#Unit 4. Cell Communication and Cell Signaling

Unbound receptors are internalized at a relatively slow rate, on average once every 30 minutes, and are recycled rapidly to the plasma membrane so there is little reduction in the total number of surface receptors. 

TLS Online TPP Program

#Id: 9626

#Unit 4. Cell Communication and Cell Signaling

Following binding of an EGF ligand, the rate of endocytosis of HER1 is increased about tenfold, and only a fraction of the internalized receptors return to the plasma membrane; the rest are degraded in lysosomes.