TrkA

Function

TrkA is the high affinity catalytic receptor for the neurotrophin, Nerve Growth Factor, or "NGF". As such, it mediates the multiple effects of NGF, which includes neuronal differentiation and survival.

The TrkA receptor is part of the large family of PI3 kinase. Despite the mistake being abundant in the scientific literature, TrkA stands for Tropomyosin-Related Kinase A and not Tyrosine Kinase A or Tyrosine Receptor Kinase A. Similarly for TrkB and TrkC, the abbreviated name has frequently been assumed to be something that it is not.

Family members

TrkA is part of a sub-family of protein kinases which includes TrkC binds and is activated by NT-3.[3]

The Low Affinity Nerve Growth Factor Receptor

There is one other NGF receptor besides TrkA, called the "Low Affinity Nerve Growth Factor Receptor"). As opposed to TrkA, the LNGFR plays a somewhat less clear role in NGF biology. Some researchers have shown the LNGFR binds and serves as a "sink" for neurotrophins. Cells which express both the LNGFR and the Trk receptors might therefore have a greater activity - since they have a higher "microconcentration" of the neurotrophin. It has also been shown, however, that in the absence of a co-expressed TrkA, the LNGFR may signal a cell to die via apoptosis - so therefore cells expressing the LNGFR in the absence of Trk receptors may die rather than live in the presence of a neurotrophin.

Role in disease

TrkA was originally cloned from a colon tumor; the cancer occurred via a translocation, which resulted in the activation of the TrkA kinase domain. However, TrkA itself does not appear to be an oncogene.

Regulation of TrkA

The levels of distinct proteins can be regulated by the "ubiquitin ligase" called NEDD-4. This mechanism may be a distinct way to control the survival of a neuron. The extent and maybe type of TrkA ubiquitiniation can be regulated by the other, unrelated receptor for NGF, p75NTR [5].

References

Further reading