Rap1 mediates sustained MAP kinase activation induced by nerve growth factor
| Autor: | Hong Yao, Randall D. York, Cindy L. Ellig, Tara J. Dillon, Philip J.S. Stork, Edwin W. McCleskey, Stephani P. Eckert |
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| Rok vydání: | 1998 |
| Předmět: |
MAP Kinase Kinase 4
MAPK7 Mitogen-activated protein kinase kinase Biology Transfection PC12 Cells MAP2K7 Mice Growth factor receptor GTP-Binding Proteins Genes Reporter Proto-Oncogene Proteins Neurites Animals Guanine Nucleotide Exchange Factors ASK1 Nerve Growth Factors MAPK14 ets-Domain Protein Elk-1 Mitogen-Activated Protein Kinase 1 Mitogen-Activated Protein Kinase Kinases Multidisciplinary MAP kinase kinase kinase Epidermal Growth Factor JNK Mitogen-Activated Protein Kinases Proteins Cell Differentiation 3T3 Cells Proto-Oncogene Proteins c-crk Cell biology Rats DNA-Binding Proteins Enzyme Activation rap GTP-Binding Proteins COS Cells Calcium-Calmodulin-Dependent Protein Kinases Mutation biology.protein Cancer research ras Proteins Matrix Metalloproteinase 3 ras Guanine Nucleotide Exchange Factors Guanosine Triphosphate Protein Kinases Platelet-derived growth factor receptor Transcription Factors |
| Zdroj: | Nature. 392(6676) |
| ISSN: | 0028-0836 |
| Popis: | Activation of mitogen-activated protein (MAP) kinase (also known as extracellular-signal-regulated kinase, or ERK)1 by growth factors can trigger either cell growth or differentiation. The intracellular signals that couple growth factors to MAP kinase may determine the different effects of growth factors: for example, transient activation of MAP kinase by epidermal growth factor stimulates proliferation of PC12 cells1, whereas they differentiate in response to nerve growth factor, which acts partly by inducing a sustained activation of MAP kinase1. Here we show that activation of MAP kinase by nerve growth factor involves two distinct pathways: the initial activation of MAP kinase requires the small G protein Ras, but its activation is sustained by the small G protein Rap1. Rap1 is activated by CRK adaptor proteins and the guanine-nucleotide-exchange factor C3G, and forms a stable complex with B-Raf, an activator of MAP kinase. Rap1 is required for at least two indices of neuronal differentiation by nerve growth factor: electrical excitability and the induction of neuron-specific genes. We propose that the activation of Rap1 by C3G represents a common mechanism to induce sustained activation of the MAP kinase cascade in cells that express B-Raf. |
| Databáze: | OpenAIRE |
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