molecular immunology Flashcards
describe one way for receptors to transmit signals
activate intracellular enzyme activity such as protein kinases = phosphorylation
phosphatatse removes phosphate groups from proteins
how receptors may be activated by factors produced by neighboring or distant cells
1) endocrine
2) paracrine
3) autocrine
4) juxtacrine
1) cytokines travel through blood to act on distant target cells
2) signalling molecules affect nearby cells e.g. CCR21 recruits cells by binding to CCR7 on T cells and DC
3) the cell produces and responds to own signalling molecule
4) direct cell to cell contact
difference between receptor and non receptor kinases
-location
-activation
-example
recetor kinase-
-membrane bound
-ligand binding brings two substrates together and they activate kinases which phosphrelate each other, leading to signals
-TGF-beta
non receptor kinase-phosphorlate target proteins but kinase is non conalently associated with the receptor
what does activation of kinase require and what is a key feature on enzymatic activity
require adaptor and scaffold proteins
-lack enzymatic activity
How Adaptor Proteins Facilitate Signal Transduction by bringing two proteins together using specialised domain
-adaptor Grb2
-signalling protein Sos
-SH3 domain
-tyrosine phosphorylated
1) the adaptor Grb2 binds to the signalling protein Sos via it’s SH3 domain
2) an activated receptor becomes tyrosine phosphorylated
3) Grb2 binds to the phosphotryosine via it’s SH2 domain, bringing Sos to the receptor
what signalling protein is important in the activation of small GTPase proteins (which act as molecular switches)
Sos
where does the signalling proteins recruit to?
what do Akt and ltK bind in plasma membrane
plasma membrane
-bind phosphorylated lipid
GTPase proteins activation and inactivation cycle and example of family
-GTP
GDP
GTP bound GTPase= active
GDP bound GTPase= inactive
ras family which controls proliferation
activation of Ras by Sos
receptor activation of Ras requires Grb2 and Sos
2 mechanisms of signal amplification
1) kinase cascade. (Ras, Raf, Mek, Erk)
2) second messenger (cAMP and calcium)
1) single Ras activates Raf, which phorphorylates Mek and activated Erk= signal amplification
2) small molecules diffuse into cells and amplify signals
-cAMP
-calcium= come extracellular or intracellular
steps in T cell receptor signalling pathway
-Lck kinase
-ITAMs
-Zap-70 kinase
-phospholipase Cy
1)Lck kinase phosphorylates ITAMS on T cell receptor
2) phosphorylated ITAMS recruit ZAP-70.
3) Lck also phosphorylated ZAP-70
-carrying the signal on
4) some effector proteins lead to activation of phospholipase Cy
what transcription factor is activated by calcium
NFAT
another example of a receptor signalling pathway
cytokine receptor
