Srcasm modulates EGF and Src-kinase signaling in keratinocytes
| Autor: | Chrysalene Schmults, Leonard M. Dzubow, Christine Marshall, John T. Seykora, Lijuan Mei, Michael Dans, Weijie Li |
|---|---|
| Rok vydání: | 2004 |
| Předmět: |
DNA Replication
Keratinocytes Cell signaling Transcription Genetic Biology Filaggrin Proteins Ligands Response Elements Biochemistry Models Biological chemistry.chemical_compound FYN Intermediate Filament Proteins Epidermal growth factor Proto-Oncogene Proteins Humans Phosphorylation Phosphotyrosine Molecular Biology Cells Cultured Adaptor Proteins Signal Transducing Cell Proliferation ets-Domain Protein Elk-1 Mitogen-Activated Protein Kinase 1 Epidermal Growth Factor Tyrosine phosphorylation Cell Differentiation Cell Biology DNA Cell biology DNA-Binding Proteins Enzyme Activation ErbB Receptors src-Family Kinases chemistry Gene Expression Regulation Cancer research biology.protein GRB2 Tyrosine kinase Proto-oncogene tyrosine-protein kinase Src Signal Transduction Transcription Factors |
| Zdroj: | The Journal of biological chemistry. 280(7) |
| ISSN: | 0021-9258 |
| Popis: | The Src-activating and signaling molecule (Srcasm) is a recently described activator and substrate of Src-family tyrosine kinases (SFKs). When phosphorylated at specific tyrosines, Srcasm associates with Grb2 and p85, the regulatory subunit of phosphoinositide 3-kinase; however, little is known about the role of Srcasm in cellular signaling. Data presented here demonstrate that epidermal growth factor (EGF) receptor ligands promote the tyrosine phosphorylation of endogenous and adenovirally transduced Srcasm in keratinocytes, and that increased levels of Srcasm activate endogenous SFKs, with a preference for Fyn and Src. In addition, Srcasm potentiates EGF-dependent signals transmitted by SFKs in keratinocytes. Tyrosine phosphorylation of Srcasm is dependent on growth factors and the activity of EGFR and SFKs. Increased Srcasm expression enhances p44/42 mitogen-activated protein kinase activity and Elk-1-dependent transcriptional events. Elevated Srcasm levels inhibit keratinocyte proliferation while promoting specific aspects of keratinocyte differentiation. Lastly, Srcasm levels are decreased in human cutaneous neoplasia. Collectively, these data demonstrate that Srcasm plays a role in linking EGF receptor- and SFK-dependent signaling to differentiation in keratinocytes. |
| Databáze: | OpenAIRE |
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