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PMID: 9003777 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't

HPK1, a hematopoietic protein kinase activating the SAPK/JNK pathway.

The EMBO journal ·Vol. 15 ·No. 24 ·1996-12-16 ·Pages 7013-25

Kiefer F, Tibbles LA, Anafi M, Janssen A, Zanke BW, Lassam N, Pawson T, Woodgett JR, Iscove NN

Abstract

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.

MeSH Terms
Amino Acid Sequence Animals Bone Marrow/enzymology COS Cells Calcium-Calmodulin-Dependent Protein Kinases/metabolism Cell Line Cloning, Molecular DNA, Complementary Enzyme Activation Gene Expression Regulation, Enzymologic JNK Mitogen-Activated Protein Kinases Mice Mitogen-Activated Protein Kinases Molecular Sequence Data Phosphorylation Protein Serine-Threonine Kinases/genetics,metabolism RNA, Messenger/genetics Sequence Homology, Amino Acid
Chemicals
DNA, Complementary RNA, Messenger hematopoietic progenitor kinase 1 Protein Serine-Threonine Kinases Calcium-Calmodulin-Dependent Protein Kinases JNK Mitogen-Activated Protein Kinases Mitogen-Activated Protein Kinases
Authors & Affiliations
9 authors, click to expand affiliations / ORCID
Kiefer F
Department of Medical Biophysics, University of Toronto, Ontario, Canada.
Tibbles L A
Anafi M
Janssen A
Zanke B W
Lassam N
Pawson T
Woodgett J R
Iscove N N
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Article Info
Journal
The EMBO journal
Abbr.
EMBO J
ISSN
0261-4189
Published
1996-12-16
Pages
7013-25
Language
English
Region
England
NLM ID
8208664
PMCID
PMC452527
Subset
IM
External Links
PubMed source PMC Full Text View journal details
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