BISC 3754 Lecture Notes - Lecture 15: Proline, Ras P21 Protein Activator 1, Phospholipid
Document Summary
Cytosolic domain either has enzyme activity of is associated with enzyme. Binding of signal molecule on extracellular side activates tyrosine kinase domain on cytosolic side. Phosphor(cid:455)latio(cid:374) of t(cid:455)rosi(cid:374)e side (cid:272)hai(cid:374)s phosphot(cid:455)rosi(cid:374)e do(cid:272)ki(cid:374)g sites for i(cid:374)tra(cid:272)ellular sig(cid:374)al proteins. Ligand binding causes receptors to dimerize (2 units join) that brings cytoplasmic kinase domains together= activation. E(cid:454): i(cid:374)suli(cid:374) (cid:271)i(cid:374)di(cid:374)g (cid:271)ri(cid:374)gs di(cid:373)ers (cid:272)lose so the(cid:455) phosphor(cid:455)late ea(cid:272)h other o(cid:374) t(cid:455)rosi(cid:374)e ki(cid:374)ase a(cid:272)ti(cid:448)e sites. In the insulin pathway, kinase domain is activated by trans-autophosphorylation. E(cid:454): epider(cid:373)al gro(cid:449)th fa(cid:272)tor (cid:894)egf(cid:895) a(cid:272)ti(cid:448)ated (cid:271)(cid:455) (cid:272)o(cid:374)for(cid:373)atio(cid:374)al (cid:272)ha(cid:374)ges (cid:271)(cid:455) i(cid:374)tera(cid:272)tio(cid:374)s (cid:271)et(cid:449)ee(cid:374) ki(cid:374)ase domains outside of the active sites. Phosphorylation at tyrosine can lead to full activation of kinase domain. Can also create docking sites for signaling proteins to bind to. No liga(cid:374)d re(cid:272)eptor is as i(cid:374)a(cid:272)ti(cid:448)e (cid:373)o(cid:374)o(cid:373)er. Dimerization orients internal kinase domain into asymmetric dimer. Egf binds= conformational changes in receptors promote dimerization of external domains.