HPK1, a hematopoietic protein kinase activating the SAPK/JNK pathway
| Autor: | F, Kiefer, L A, Tibbles, M, Anafi, A, Janssen, B W, Zanke, N, Lassam, T, Pawson, J R, Woodgett, N N, Iscove |
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| Rok vydání: | 1996 |
| Předmět: |
DNA
Complementary Sequence Homology Amino Acid Molecular Sequence Data JNK Mitogen-Activated Protein Kinases Protein Serine-Threonine Kinases Gene Expression Regulation Enzymologic Cell Line Enzyme Activation Mice Bone Marrow COS Cells Calcium-Calmodulin-Dependent Protein Kinases Animals Amino Acid Sequence RNA Messenger Cloning Molecular Mitogen-Activated Protein Kinases Phosphorylation Research Article |
| Zdroj: | The EMBO journal. 15(24) |
| ISSN: | 0261-4189 |
| Popis: | In mammalian cells, a specific stress-activated protein kinase (SAPK/JNK) pathway is activated in response to inflammatory cytokines, injury from heat, chemotherapeutic drugs and UV or ionizing radiation. The mechanisms that link these stimuli to activation of the SAPK/JNK pathway in different tissues remain to be identified. We have developed and applied a PCR-based subtraction strategy to identify novel genes that are differentially expressed at specific developmental points in hematopoiesis. We show that one such gene, hematopoietic progenitor kinase 1 (hpk1), encodes a serine/threonine kinase sharing similarity with the kinase domain of Ste20. HPK1 specifically activates the SAPK/JNK pathway after transfection into COS1 cells, but does not stimulate the p38/RK or mitogen-activated ERK signaling pathways. Activation of SAPK requires a functional HPK1 kinase domain and HPK1 signals via the SH3-containing mixed lineage kinase MLK-3 and the known SAPK activator SEK1. HPK1 therefore provides an example of a cell type-specific input into the SAPK/JNK pathway. The developmental specificity of its expression suggests a potential role in hematopoietic lineage decisions and growth regulation. |
| Databáze: | OpenAIRE |
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