What is the ligand for EGFR?
Betacellulin. Betacellulin (BTC) is a dual-specificity ligand that binds to and activates EGFR and ERBB4.
Is EGFR a transcription factor?
EGFR might, therefore, function as a transcription factor to activate genes required for cell proliferation. These results challenge the textbook dogma that receptor tyrosine kinases stimulate mitogenic pathways only through sustained activation of second messenger cascades at the plasma membrane or in endosomes.
Are EGFR mutations dominant or recessive?
The EGFR gene is associated with autosomal dominant predisposition to lung cancer (MedGen UID: 472093).
How long do EGFR inhibitors work?
EGFR inhibitors that target cells with the T790M mutation EGFR inhibitors can often shrink tumors for several months or more. But eventually these drugs stop working for most people, usually because the cancer cells develop another mutation in the EGFR gene. One such mutation is known as T790M.
How is ligand-mediated activation of EGFR achieved?
Crystallography studies have revealed that ligand-mediated EGFR activation is achieved by a conformational change in the extracellular domain of the receptor upon ligand binding, resulting in receptor dimerization and internalization [6].
What happens to EGFR once in the nucleus?
Once in the nucleus, EGFR can either behave as a proper transcription factor (for cyclin D1 up-regulation) or as coregulator of other gene transactivators. Both pathways result in nuclear activation of genes related with cell proliferation, survival, invasion, and metastasis.
Can a unliganded EGF receptor be internalized?
Unliganded EGFR can also be internalized but at a 10-fold slower rate than EGF-stimulated receptor [7], but the dimerization and activation states of these receptors are unclear. Crucial to RTK activation is the formation of an asymmetric dimer of kinase domains [8].
Where does ligand independent receptor activation take place?
Ligand-independent receptor activation occurs in some tumors that display forms of the EGFR and HER that have a deletion of the extracellular domain that result in constitutive receptor activation ( 5, 6 ).