Neurotrophin/TRK Signaling

Neurotrophins are growth factors that control survival, development and function of neurons in the central and peripheral nervous system. Four mammalian neurotrophins have been described: nerve growth factor (NGF), brain-derived neurotrophic factor (BDNF), neurotrophin-3 (NT-3), and neurotrophin-4 (NT-4). Neurotrophins can bind members of the tropomyosin-related kinase (TRK) family of receptors as well as p75 neurotrophin receptor p75(NTR).TRKs are tyrosine kinases that are activated by the binding of neurotrophins. Signal transduction involves the recruitment of adapter molecules Shc, GRB2 and GAB1 which in turn activate the Ras/Raf/MEK/ERK pathway and the PI3K/AKT pathway. TRKs also activate PLCγ1 which increases intracellular Ca+2. Neurotrophin signaling via TRKs effects neuron proliferation and neurite outgrowth and differentiation.p75NTR is a member of the tumour necrosis factor receptor superfamily. Stimulation of p75NTR with neurotrophin can activate multiple downstream signals, including Rho-like GTPases Cdc42 and the stress activated kinase, JNK. p75NTR is involved in a diverse array of cellular responses, including apoptosis, growth and myelination.