CHARACTERIZATION OF TROPOMYOSIN-RELATED RECEPTOR KINASE A (TRKA) SIGNALING

University Of California, San Francisco, San Francisco CA

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Abstract

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Nerve growth factor (NGF) is a signaling molecule, originally discovered for its role on differentiation and survival of peripheral sensory and sympathetic neurons. The activation of the receptor tyrosine kinase, TrkA, by the NGF leads to the phosphorylation of several tyrosines in the intracellular part of the receptor. Two phosphotyrosines located at 490 and 785 create docking sites for adaptator or effector proteins which stimulate several signaling pathways. My research interest is focused in characterizing the phosphoproteome specifically activated by these 2 phosphotyrosines by using mutant receptors. Moreover, the use of a chimeric receptor (extracellular part of the PDGF receptor/intracellular part of TrkA) allows the identification of the signaling pathways specific of TrkA and not of p75NTR. I am also interested in characterizing the direct substrates of the tyrosine kinase domain of TrkA. The kinase engineered to use synthetic ATP analogs specifically thiophosphorylates its substrates. This thiophosphorylation modification provides a tag that can be used to affinity purify and identify labeled proteins. This project will further understanding of the function of the NGF receptor in neurons.