von Willebrand factor deficiency likewise causes a bleeding disorder (von Willebrand disease) by reducing platelet adhesion and by lowering plasma factor VIII

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.

TLS Online TPP Program

#Id: 9627

#Unit 4. Cell Communication and Cell Signaling

Monoubiquitinylation of the HER1 cytosolic domain by the E3 ubiquitin ligase c-Cbl

TLS Online TPP Program

#Id: 9628

#Unit 4. Cell Communication and Cell Signaling

c-Cbl 

adds a single ubiquitin to a given lysine of a protein

TLS Online TPP Program

#Id: 9629

#Unit 4. Cell Communication and Cell Signaling

c-Cbl contains: 

a domain that binds directly to phosphorylated EGF receptors

a RING finger domain, which recruits ubiquitin-conjugating enzymes and mediates transfer of ubiquitin to the receptor