A novel src homology 3 domain-containing adaptor protein, HIP-55, that interacts with hematopoietic progenitor kinase 1.

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.
Mesh Terms:
Amino Acid Sequence, Binding Sites, Carrier Proteins, Cell Line, Cloning, Molecular, DNA, Complementary, Enzyme Activation, Female, Gene Expression, HL-60 Cells, Hela Cells, Humans, Immunoblotting, JNK Mitogen-Activated Protein Kinases, Male, Microfilament Proteins, Mitogen-Activated Protein Kinases, Molecular Sequence Data, Mutation, Proline, Protein Binding, Protein-Serine-Threonine Kinases, Recombinant Fusion Proteins, Sequence Homology, Amino Acid, Tissue Distribution, Two-Hybrid System Techniques, src Homology Domains
J. Biol. Chem.
Date: Nov. 26, 1999
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