Autocatalytic phosphorylation of FGFR3 t(4;14) translocation mutants

Stable Identifier
R-HSA-2038387
Type
Reaction [transition]
Species
Homo sapiens
Compartment
plasma membrane, cytosol
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Autocatalytic phosphorylation of FGFR3 t(4;14) translocation mutants
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Overexpression of WT FGFR3 is weakly transforming when expressed in a mouse haematopoietic model, while expression of translocated FGFR3 carrying activating point mutations in the coding sequence is strongly transforming in both NIH 3T3 cells and the haematopoietic mouse model (Chesi, 2001; Ronchetti, 2001; Li, 2001). Activating mutations in FGFR3 are mutually exclusive with activating Ras mutations, and focus formation in NIH 3T3 cells is inhibited by cotransfection with dominant negative forms of ras or raf, suggesting that activation of the MAPK pathway is the primary oncogenic event in translocated myeloma lines (Chesi, 2001). Inhibition of FGFR3 in multiple myeloma lines and tumors has been shown to inhibit proliferation (Grand, 2004; Qing, 2009; Trudel, 2009; Krejci, 2010)

Literature References
PubMed ID Title Journal Year
19381019 Antibody-based targeting of FGFR3 in bladder carcinoma and t(4;14)-positive multiple myeloma in mice

Qing, J, Du, X, Chen, Y, Chan, P, Li, H, Wu, P, Marsters, S, Stawicki, S, Tien, J, Totpal, K, Ross, S, Stinson, S, Dornan, D, French, D, Wang, QR, Stephan, JP, Wu, Y, Wiesmann, C, Ashkenazi, A

J Clin Invest 2009
20439987 NF449 is a novel inhibitor of fibroblast growth factor receptor 3 (FGFR3) signaling active in chondrocytes and multiple myeloma cells

Krejci, P, Murakami, S, Prochazkova, J, Trantirek, L, Chlebova, K, Ouyang, Z, Aklian, A, Smutny, J, Bryja, V, Kozubik, A, Wilcox, WR

J Biol Chem 2010
15029211 Targeting FGFR3 in multiple myeloma: inhibition of t(4;14)-positive cells by SU5402 and PD173074

Grand, EK, Chase, AJ, Heath, C, Rahemtulla, A, Cross, NC

Leukemia 2004
11290605 The myeloma-associated oncogene fibroblast growth factor receptor 3 is transforming in hematopoietic cells

Li, Z, Zhu, YX, Plowright, EE, Bergsagel, PL, Chesi, M, Patterson, B, Hawley, TS, Hawley, RG, Stewart, AK

Blood 2001
16467200 The inhibitory anti-FGFR3 antibody, PRO-001, is cytotoxic to t(4;14) multiple myeloma cells

Trudel, S, Stewart, AK, Rom, E, Wei, E, Li, ZH, Kotzer, S, Chumakov, I, Singer, Y, Chang, H, Liang, SB, Yayon, A

Blood 2006
11429702 Deregulated FGFR3 mutants in multiple myeloma cell lines with t(4;14): comparative analysis of Y373C, K650E and the novel G384D mutations

Ronchetti, D, Greco, A, Compasso, S, Colombo, G, Dell'Era, P, Otsuki, T, Lombardi, L, Neri, A

Oncogene 2001
11157491 Activated fibroblast growth factor receptor 3 is an oncogene that contributes to tumor progression in multiple myeloma

Chesi, M, Brents, LA, Ely, SA, Bais, C, Robbiani, DF, Mesri, EA, Kuehl, WM, Bergsagel, PL

Blood 2001
Participants
Input
Output
Participant Of
hasEvent
Catalyst Activity
Catalyst Activity
Title
protein tyrosine kinase activity of FGFR3 (4;14) translocation mutant dimers [plasma membrane]
Physical Entity
FGFR3 (4;14) translocation mutant dimers [plasma membrane]
Activity
protein tyrosine kinase activity (0004713)
Disease
Name Identifier Synonyms
cancer 162 malignant tumor, malignant neoplasm, primary cancer
multiple myeloma 9538
Authored
Rothfels, K  (2012-02-10)
Reviewed
Ezzat, S  (2012-05-15)
Created
Rothfels, K  (2012-01-10)