The TrK receptor family

Abstract

The Trk family is composed of three principal members (A, B and C), also termed neurotrophin tyrosine kinase receptors (NTRK1, NTRK2, NTRK3), with several additional splice variants, which in humans are located on three different chromosomes (1, 9, 15). The Trk proteins are receptors for the neurotrophin family of growth factors (NGF, BDNF, NT-3, and NT4/5); they also bind and respond more weakly to the proforms of these neurotrophins. Both the neurotrophins and pro-neurotrophins utilize other receptors (p75NTR, sortilin) that can interact with the Trks and affect their activity. The Trks are predominantly expressed in nervous tissues, where they are essential for the growth, development, and maintenance of select types of both peripheral and central neurons and are involved in neurodegenerative diseases. The Trks are also found in some nonneuronal tissues and in a wide variety of tumors, where they can play an active role in tumor progression and metastasis. The activated Trk receptors primarily bind and signal through Shc, FRS2, and PLCγ, which in turn activate PI3K, the Erks, and the hydrolysis of inositol phospholipids, among other events, leading to the modulation of gene transcription.