Kinase Linked receptors Flashcards
Name the 5 main types of enzyme-linked receptors
RTKs Receptor Serine/Threonine kinase Tyrosine Kinase-associated receptors Receptor Guanylyl Cyclases Receptor Tyrosine Phosphatases
What do RTKs transduce signals to ?
polypeptide + protein hormones
growth factors
Describe how RTKs are activated
- ligand binds to receptor
- conformational change
- tyrosine kinase is phosphorylated
- the signalling proteins activate the receptor
Name a type of RTK
EGFR (epidermal growth factor receptor)
What does drysregulation of EF/EGFR expression lead to?
cancer development
What does EGF/EGFR signalling promote?
- embryonic development
- stem cell regeneration
- regulation of ion transport
- wound healing
Describe the typical structure of an RTK e.g. EGFR
- extracellular LBD
- TM helix domain
- intracellular catalytic/tyrosine kinase domain
- juxtamembrane + adaptor domains with tyrosine residues
Define dimerization
combination of two identical molecules to form a dimer
Binding of EGR causes the ______ of EGFR monomers leading to a ______ change. This triggers trans + auto-___________ of tyrosine residues, which initiate signalling cascades
dimerization
conformational
phosphorylation
What are the 2 main downstream signalling pathways triggered by activated EGFRs?
- RAS/MAPK
- PI3K/AKT
What are RTKs key regulators of?
- proliferation
- differentiation
- cell survival + metabolism
- cell migration
- cell cycle control
Tyrosine Kinase-associated receptors transduce signals to _____
cytokines
What cells produce cytokines?
immune cells
What are the functions of cytokines?
- cell communication
- cell development
- differentiation
- immune + inflammatory response
Name a cytokine receptor signalling pathway
JAK/STAT
What are JAKs?
family of non-receptor tyrosine protein kinases that convert stimuli into cellular processes
What are STATs?
A family of transcription factors + SH2 domain proteins
Oncogenic transformation may result from loss of auto-control mechanisms via what
- mutation
- over-expression of receptor
- increased autocrine signalling
Describe the 2 major classes of EGFR targeted anticancer therapies
- Tyrosine kinase inhibitors (TKIs) - ATP mimetics bind to receptor kinases’s pocket excluding ATP + preventing signal transduction
- Humanised monoclonal antibodies against EGFR extracellular domain that block ligand binding
Give an example of a TKI drug used in anticancer therapy
lapatinib
Give an example of a monoclonal antibody drug used in anticancer therapy
cetuximab
What can the dysregulation of JAK/STAT signalling cause to develop?
- cancer
- immune/inflammatory disorders e.g. psoriasis
Name 3 JAK inhibitors developed to treat immune/inflammatory disorders
- Tofacitinib - inhibits JAK1 + 3 inhibitor
- Baricitinib - inhibits JAK1 + 2
- Ruxolitinib - inhibits JAK1 + 2
What is an enzyme linked receptor?
transmembrane protein with enzyme activity/direct association with an enzyme
How do kinase linked enzymes work?
- bind to ligand leading to a conformational change
- transmitted to TM helix
- enzyme activated
- signalling cascade initiated
What 3 things do kinase - linked receptors play a major role in?
cell growth
proliferation
differentiation
