Abstract
Hematopoietic progenitor kinase 1 (HPK1) is a member of the mitogen-activated protein kinase kinase kinase kinase (MAP4K) family and an upstream activator of the c-Jun N-terminal kinase (JNK) signaling cascade. HPK1 interacts, through its proline-rich domains, with growth factor receptor-bound 2 (Grb2), CT10-regulated kinase (Crk), and Crk-like (CrkL) adaptor proteins. We identified a novel HPK1-interacting protein of 55 kDa (HIP-55), similar to the mouse SH3P7 protein, containing an N-terminal actin-binding domain and a C-terminal Src homology 3 domain. We found that HPK1 bound to HIP-55 both in vitro and in vivo. When co-transfected, HIP-55 increased HPK1's kinase activity as well as JNK1's kinase activity. A dominant-negative HPK1 mutant blocked activation of JNK1 by HIP-55 showing that HIP-55 activates the JNK1 signaling pathway via HPK1. Our results identify a novel protein, HIP-55, that binds to HPK1 and regulates the JNK1 signaling cascade.
Publication types
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Amino Acid Sequence
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Binding Sites
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Carrier Proteins / chemistry
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Carrier Proteins / genetics
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Carrier Proteins / metabolism*
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Cell Line
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Cloning, Molecular
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DNA, Complementary / genetics
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Enzyme Activation
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Female
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Gene Expression
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HL-60 Cells
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HeLa Cells
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Humans
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Immunoblotting
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JNK Mitogen-Activated Protein Kinases
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Male
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Microfilament Proteins*
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Mitogen-Activated Protein Kinases / metabolism
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Molecular Sequence Data
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Mutation
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Proline / genetics
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Proline / metabolism
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Protein Binding
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Protein Serine-Threonine Kinases / genetics
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Protein Serine-Threonine Kinases / metabolism*
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Recombinant Fusion Proteins / genetics
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Recombinant Fusion Proteins / metabolism
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Sequence Homology, Amino Acid
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Tissue Distribution
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Two-Hybrid System Techniques
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src Homology Domains / genetics*
Substances
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Carrier Proteins
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DBNL protein, human
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DNA, Complementary
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Microfilament Proteins
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Recombinant Fusion Proteins
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Proline
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hematopoietic progenitor kinase 1
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Protein Serine-Threonine Kinases
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JNK Mitogen-Activated Protein Kinases
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Mitogen-Activated Protein Kinases