Dimerization of FGFR4 mutants with enhanced kinase activity

Stable Identifier
Reaction [transition]
Homo sapiens
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FGFR4 is highly expressed in rhabdomyosarcoma (RMS) tissue, and high levels of expression are correlated with lower survival. Sequencing of exons from 94 RMS tumors identified 14 missense variants, 6 of which were localized in the tyrosine kinase domain, and four of which were in two amino acids (N535K/D and V550E/L). Mutations at amino acid 535 are predicted to eliminate an inhibitory H-bond that restricts receptor autophosphorylation, and mutations at amino acid 550 are believed to alter the ATP-binding site. Functional studies on N535K and V550 show that they undergo autophosphorylation when transfected into a murine RMS lines and transformed NIH 3T3 cells, leading to a metastatic phenotype (Taylor, 2009).

Literature References
PubMed ID Title Journal Year
19809159 Identification of FGFR4-activating mutations in human rhabdomyosarcomas that promote metastasis in xenotransplanted models

Chanock, SJ, Cheuk, AT, Catchpoole, D, Desai, K, Chung, JY, Chen, QR, Hewitt, SM, Fang, J, Helman, LJ, Khan, J, Kim, S, Merlino, G, Khanna, C, Mendoza, A, Ngo, V, Tsang, PS, Staudt, LM, Taylor JG, 6th, Song, YK, Shah, K, Qualman, SJ, Wei, JS, Yeung, C, Youngblood, V, Yu, Y

J Clin Invest 2009
Normal reaction
Functional status

Gain of function of FGFR4 enhanced kinase mutants [plasma membrane]

Name Identifier Synonyms
rhabdomyosarcoma DOID:3247 Rhabdomyosarcoma NOS (morphologic abnormality), rhabdomyosarcoma, Rhabdomyosarcoma, no subtype (morphologic abnormality), rhabdomyoblastoma, Rhabdomyosarcoma (disorder)
cancer DOID:162 malignant tumor, malignant neoplasm, primary cancer
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