Cell signalling 3

What is an example of enzyme-coupled receptor?

receptor tyrosine kinases (RTKs) and have a tyrosine kinase on the cytoplasmic side

Explain the MAPK pathway?

Ligand binding (growth factor) causes receptor to dimerise

this causes activation due to autophosphorylation

phosphorylated sites on RTK act as binding sites for proteins with SH2 domain, form signalling complexes

Proteins activate Ras a GTPase

Ras phosphorylates Mek a mitogen activated protein (MAP) kinase kinase, which phosphorylates a MAP kinase, which phosphorylates transcription factors for cell proliferation

What is the VEGF ligand/receptor that needs to be known?

VEGF-A and VEGFR2

What is the process of VEGF signalling?

VEGF-A binds to VEGFR2 forming dimer

receptor is activated by autophosphorylation

form signalling complexes

What is angiogenesis?

Formation of new capillaries from blood vessels by proliferation

How does VEGF affect angiogenesis?

Endothelial cells exposed to VEGF become tip cells

Begin sprouting via filopodia

forms a lumen and blood flow established

stabilised via pericytes

How does hypoxia effect angiogenesis?

HIF-1alpha is transcription factor that increases transcription of VEGF

in oxygen HIF-1alpha is degraded but in low oxygen HIF-1alpha is translocated causing more VEGF and angiogenesis

Why is VEGF crucial?

Regulates body growth, kidney function and vasculogenesis

What can occur due to too much VEGF?

Tumours use VEGF to maintain and grow

How to inhibit VEGF?

anti-VEGF/VEGFR monoclonal antibodies

RTK inhibitors

thrombosis is side affect of this

What can low levels of VEGF cause?

Low levels of VEGF impair spinal cord perfusion and insufficient neuroprotection

causes onset of nervous degeneration