D. Ensenat et al., A novel Src homology 3 domain-containing adaptor protein, HIP-55, that interacts with hematopoietic progenitor kinase 1, J BIOL CHEM, 274(48), 1999, pp. 33945-33950
Hematopoietic progenitor kinase 1 (HPK1) is a member of the mitogen-activat
ed protein kinase kinase kinase kinase (MAP4K) family and an upstream activ
ator of the c-Jun N-terminal kinase (JNK) signaling cascade. HPK1 interacts
, through its proline-rich domains, with growth factor receptor-bound 2 (Gr
b2), 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 JNK
1 signaling pathway via HPK1. Our results identify a novel protein, HIP-55,
that binds to HPK1 and regulates the JNK1 signaling cascade.