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

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

J Biol Chem 2010
19381019 Antibody-based targeting of FGFR3 in bladder carcinoma and t(4;14)-positive multiple myeloma in mice

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

J Clin Invest 2009
15029211 Targeting FGFR3 in multiple myeloma: inhibition of t(4;14)-positive cells by SU5402 and PD173074

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

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

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

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

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

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

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

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

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

Blood 2001
Participants
Input
Output
Participates
as an event of
Catalyst Activity

protein tyrosine kinase activity of FGFR3 (4;14) translocation mutant dimers [plasma membrane]

Physical Entity
FGFR3 (4;14) translocation mutant dimers [plasma membrane] (Homo sapiens)
Activity
protein tyrosine kinase activity (GO:0004713)
Functional status

Gain of function of FGFR3 (4;14) translocation mutant dimers [plasma membrane]

Disease Entity
Status
Disease
Name Identifier Synonyms
multiple myeloma DOID:9538
cancer DOID:162 malignant tumor, malignant neoplasm, primary cancer
Authored
Rothfels, K  (2012-02-10)
Reviewed
Ezzat, S  (2012-05-15)
Created
Rothfels, K  (2012-01-10)
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