Vignais, M. L., Sadowski, H. B., Watling, D., Rogers, N. C., Gilman, M. (April 1996) Platelet-derived growth factor induces phosphorylation of multiple JAK family kinases and STAT proteins. Molecular and Cellular Biology, 16 (4). pp. 1759-69. ISSN 0270-7306
Abstract
Receptors for interferons and other cytokines signal through the action of associated protein tyrosine kinases of the JAK family and latent cytoplasmic transcription factors of the STAT family. Genetic and biochemical analysis of interferon signaling indicates that activation of STATs by interferons requires two distinct JAK family kinases. Loss of either of the required JAKs prevents activation of the other JAK and extinguishes STAT activation. These observations suggest that JAKs provide interferon receptors with a critical catalytic signaling function and that at least two JAKs must be incorporated into an active receptor complex. JAK and STAT proteins are also activated by ligands such as platelet-derived growth factor (PDGF), which act through receptors that possess intrinsic protein tyrosine kinase activity, raising questions about the role of JAKs in signal transduction by this class of receptors. Here, we show that all three of the ubiquitously expressed JAKs--JAK1, JAK2, and Tyk2--become phosphorylated on tyrosine in both mouse BALB/c 3T3 cells and human fibroblasts engineered to express the PDGF-beta receptor. All three proteins are also associated with the activated receptor. Through the use of cell lines each lacking an individual JAK, we find that in contrast to interferon signaling, PDGF-induced JAK phosphorylation and activation of STAT1 and STAT3 is independent of the presence of any other single JAK but does require receptor tyrosine kinase activity. These results suggests that the mechanism of JAK activation and JAK function in signaling differs between receptor tyrosine kinases and interferon receptors.
| Item Type: | Paper |
|---|---|
| Uncontrolled Keywords: | 3T3 Cells Animals DNA-Binding Proteins/ metabolism Enzyme Activation/drug effects Humans Mice Mice, Inbred BALB C Phosphorylation Platelet-Derived Growth Factor/ pharmacology Protein-Tyrosine Kinase/ metabolism Proto-Oncogene Proteins Receptors, Platelet-Derived Growth Factor/drug effects/ metabolism Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S. STAT1 Transcription Factor STAT3 Transcription Factor Signal Transduction Trans-Activators/ metabolism Tumor Cells, Cultured Tyrosine/metabolism |
| Subjects: | bioinformatics > genomics and proteomics > genetics & nucleic acid processing > protein structure, function, modification > protein types > DNA binding protein bioinformatics > genomics and proteomics > genetics & nucleic acid processing > protein structure, function, modification > protein types > epidermal growth factor bioinformatics > genomics and proteomics > genetics & nucleic acid processing > protein structure, function, modification > protein expression > phosphorylation organs, tissues, organelles, cell types and functions > tissues types and functions > signal transduction bioinformatics > genomics and proteomics > genetics & nucleic acid processing > protein structure, function, modification > protein types > enzymes > kinase > tyrosine kinase |
| CSHL Authors: | |
| Communities: | CSHL labs |
| Depositing User: | Kathleen Darby |
| Date: | April 1996 |
| Date Deposited: | 12 May 2014 16:39 |
| Last Modified: | 12 May 2014 16:39 |
| PMCID: | PMC231162 |
| Related URLs: | |
| URI: | https://repository.cshl.edu/id/eprint/30121 |
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