Signal Transduction 3 Flashcards
receptors basic categories
1-Ligand gated channels
2-Plasma membrane receptors
—-linked to g proteins
—-linked to protein kinase
3-Nuclear protein
linked to protein kinase (plasma membrane)
RTK–Receptor Tyrosine Kinases
GPCR regulate
Shorter term metabolic changes
RTK regulate
differentiation, cell division, survival
signal that stimulate dividing cells is
growth factor
many growth factor share a common theme
1-growth factor binding result in dimerization of receptors
2-trans-auto-phosphorylate of cytoplasmic domain does not phosphorylate itself, phosphorylate the neighbor
3-cytoplasmic signalling activated by binding to phosphorylated tyrosine
cytoplasimic signalling molecules associate with receptors by
SH2 and PTB domains
SH2
amino acids chains contain binding pocket that interact with pTyr
Adaptors
act as linkers enabling
contain SH2/PTB domain
Additional protein-protein interaction
Adaptors with SH2 domain
GRB2 bind to RTK
SH3 domain associated with Sos
Adaptor with PTB domain
IRS bind with RTK
lead to phosphorylation of IRS tyrosine
pTyr act as scaffolding for SH@ enzymes
Effectors
1- STAT family
2- Signalling enzymes with SH2 Domains wich can directly bind to RTK
STAT family
SH2 domain STAT bind to RTK, phosphrylate tyrosine in STAT, allow STAT dmierize, forming functional tanscription factor, trnaslocate to nucleus
signalling enzyme (with Sh2 doamin and ability to bind with RTK
protein kinases
shp2
plc
GAPs
signalling enzyme mechanism
1- recruitment of enzyme
2-binding of pTyr can result in conformational changes in catalytic domain
3- phosphorylation of enzyme can increase/decrease catalytic activity
Termination
RTK doesn’t require Arrestin (GPCR need arrestin)
they have short motif interacting with AP2