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Translocated in liposarcoma (TLS) is a substrate for fibroblast growth factor receptor-1
Peter Klint1, Ulf Hellman, Christer Wernstedt
1Rudbeck Laboratory, Department of Genetics and Pathology, 751 85, Uppsala, Sweden.
Abstract:
Binding of fibroblast growth factor (FGF) to the high affinity receptor-1 (FGFR-1) leads to activation of its endogenous tyrosine kinase activity. A number of substrates for the FGFR-1 kinase have been identified. Among those, FGF receptor-substrate-2 (FRS-2) was identified by virtue of its interaction with p13suc, a yeast protein involved in cell cycle regulation. We have used immobilized p13suc to identify a new substrate for FGRF-1, which is identical to "translocated in liposarcoma" (TLS). TLS is a RNA/DNA-binding protein which occurs in fusion products with different transcription factors in a variety of solid tumours. We show that TLS is tyrosine phosphorylated in intact cells by a number of different growth factors, indicating a role in growth regulation.
Insights
Fibroblast growth factor receptor-1 (FGFR-1) phosphorylates translocated in liposarcoma (TLS). This RNA/DNA-binding protein is implicated in growth regulation and cancer, suggesting a new role for FGFR-1 signaling in tumor development.
Area of Science:
- Molecular Biology
- Cell Signaling
- Oncology
Background:
- Fibroblast growth factor (FGF) binding to fibroblast growth factor receptor-1 (FGFR-1) activates its tyrosine kinase activity.
- Several FGFR-1 substrates, including FGF receptor-substrate-2 (FRS-2), are known.
- FRS-2 was identified via interaction with yeast protein p13suc, involved in cell cycle regulation.
Purpose of the Study:
- To identify novel substrates of FGFR-1 kinase activity.
- To investigate the role of the translocated in liposarcoma (TLS) protein in growth regulation.
Main Methods:
- Utilized immobilized p13suc to screen for interacting proteins.
- Performed tyrosine phosphorylation assays in intact cells stimulated with growth factors.
Main Results:
- Identified "translocated in liposarcoma" (TLS) as a novel substrate for FGFR-1.
- TLS, an RNA/DNA-binding protein found in tumor-associated fusion products, is tyrosine phosphorylated by multiple growth factors.
- Demonstrated TLS tyrosine phosphorylation in intact cells.
Conclusions:
- TLS is a direct substrate of FGFR-1 kinase.
- TLS tyrosine phosphorylation by growth factors suggests its involvement in cellular growth regulation.
- These findings highlight a potential role for TLS in growth factor-mediated signaling pathways relevant to cancer.
