Cell Signalling 2 Flashcards
calcium as a second messenger
+ storage + stimulated by
- stored in extracellular/intracellular (mainly ER)
- enter cytoplasm thru ion channels
- stimulated by other 2nd messengers (cAMP, IP3)
intracellular tyrosine kinase domain function
phosphorylates tyrosines
(autophosphorylation)
guanylyl cyclase function
makes cyclic GMP
two examples of RTKs
RTKs → receptors tyrosine kinases
EGF & insulin
EGF = epidermal growth factor
explain how RTKs act via Ras & MAPK cascades
MAPK = mitogen activated protein kinase
RTK → Ras → Raf → MAPK pathway
* 3 tiered kinase signalling pathways
* MAPK kinase kinase = MAPK kinase = MAPK = downstream target proteins (TFs) → cellular response
= means “phosphorylates”
→ means “activates”
function of phosphorylation by MAPK
- acts as a switch to turn on or turn off activity of substrate proteins
- part of phosphorelay system
difference between heterotrimeric G-proteins and Ras
Ras = monomeric
which proteins modulate Ras function
GEF & GAP
GEF = guanine nucleotide exchange factor
GAP = GTPase activating protein
phosphatases
remove phosphate groups
role of kinases & protein phosphorylation in signal transduction (4)
- proteins (incl TFs) regulated by phosphorylation
- some receptors have kinase domains
- some receptors recruit kinases directly
- some receptors use secondary messengers to activate kinases
signals are amplified during signal transduction by….
enzymes
what does failure to switch off G-protein lead to?
disease
e.g. cholera toxin irreversibly modifies G proteins
Ras oncogene
mutant form of RAS
- are constitutively activated
normal = inactive until activated by growth factors
another 2 classes of molecules PCRs bind to
- GRKs → family of protein kinases
- β-arrestins → family of adaptor & scaffolding proteins
GRKs → GPCR kinases
work together to desensitise GPCRs
what inhibits rhodopsin
rhodopsin kinase