Tropomyosin receptor kinase A–CD44 variant 3 protein–protein interface (TrkA–CD44v3 PPI)

The Tropomyosin receptor kinase A (TrkA)–CD44 variant 3 (CD44v3) protein–protein interface is a specialized signaling complex where the CD44v3 isoform acts as a co-receptor for TrkA, the high-affinity receptor for Nerve Growth Factor (NGF) [Bourguignon et al., 2002, J Biol Chem]. CD44v3 physically associates with TrkA, facilitating the recruitment of NGF and significantly enhancing the receptor's tyrosine kinase activity [UniProt P04629, P16070]. This interaction is particularly prominent in malignant cells, where it triggers downstream signaling cascades such as the PLC-gamma1 and MAPK pathways [Bourguignon et al., 2005, J Cell Sci]. These pathways are critical drivers of tumor cell proliferation, migration, and cytoskeletal reorganization, contributing to an aggressive cancer phenotype [Montgomery et al., 2003, J Biol Chem]. In diseases like head and neck squamous cell carcinoma (HNSCC), the overexpression of CD44v3 and its coupling with TrkA are linked to increased metastatic potential and poor prognosis [Bourguignon et al., 2002]. Targeting this specific protein-protein interaction offers a therapeutic strategy to selectively inhibit oncogenic TrkA signaling while potentially sparing the physiological functions of TrkA in the nervous system. Experimental approaches to disrupt this interface include the use of competitive peptides, such as the B6 peptide, which have shown efficacy in reducing tumor growth and migration in preclinical models [Bourguignon et al., 2002].

Other names

TrkA-CD44v3 complexNTRK1-CD44v3 interactionCD44v3-TrkA signaling complexp140TrkA-CD44v3 interaction

Disruption of the physical association between the CD44v3 isoform and the TrkA receptor to inhibit Nerve Growth Factor (NGF)-induced tyrosine kinase activation and downstream oncogenic signaling pathways [Bourguignon et al., 2002].