2009 Group 4 Project

From CellBiology

== Tyrosine Receptor Kinases (Trk) ==

Introduction

Trk receptors are a family of tyrosine kinases commonly associated with growth and function regulation in neuronal cells. Binding of ligands to Trks can effect growth, plasticity and synaptic strength of neuronal junctions - although it is notable that Ligand binding does not itself illicit an action potential event.

Structure

  • TrK receptors act as dimeric transmembrane proteins. Distally, three cysteine-rich motiffs and two Leucine rich regions form a conserved NGF binding region which is common to all TrK's near the amino terminus(in addition, TrkA is possesed of an additional NGF binding region, see TrK A).
  • Additionally, the common binding region is flanked by a pair of extracelluar immunoglobin-like domains located proximally to the cell membrane. The juxtamembrane complex contains a variable amino acid sequence suggested to determine ligand bindng affinity and specificiy and may bind directly to some ligands; The localization of these peptides appears to be non-specific in tertiary NGF-TrKA complex structures however their conformation within this complex appears to indicate direct participation in complex binding.
  • Further NGF binding site affinity is generated through collaboration with the p75 protein/neurotrophin receptor (p75NTR). Furthermore, p75NTR regulates NT-3-TrkA and NT-4/5-TrkB mediated receptor activation by blocking Neurotropin ligation by circumnavigating the prequisite of these neurotropins for receptor activation.

Function

Trk's play numerous physiological roles in regulation of neuronal cell function:

Matainence and Proliferation of undifferentiated Cell Lines

Dynamic Process

NGF binding to ligation region facilitates dimerisation of Trk Receptor monomers into the signal tranductive unit- activating the kinase unit. Phosphorylation of the autoregulatory loop tyrosines of the cytoplasmic domain further activates the kinase. Phosphorylation of an additional seven tyrosines within this region promotes signalling by providing docking sides for adaptor proteins which regulate signalling-cascade couples.

Current Research

Timeline

References

Glossary

2009 Group Projects

--Mark Hill 14:02, 19 March 2009 (EST) Please leave these links to all group projects at the bottom of your project page.

Group 1 Meiosis | Group 2 Cell Death - Apoptosis | Group 3 Cell Division | Group 4 Trk Receptors | Group 5 The Cell Cycle | Group 6 Golgi Apparatus | Group 7 Mitochondria | Group 8 Cell Death - Necrosis | Group 9 Nucleus | Group 10 Cell Shape