Human HPK1, a novel human hematopoietic progenitor kinase that activates the JNK/SAPK kinase cascade.
The c-Jun amino-terminal kinases (JNKs)/stress-activated protein kinases (SAPKs) play a crucial role in stress responses in mammalian cells. The mechanism underlying this pathway in the hematopoietic system is unclear, but it is a key in understanding the molecular basis of blood cell differentiation. We have cloned a novel protein kinase, termed hematopoietic progenitor kinase 1 (HPK1), that is expressed predominantly in hematopoietic cells, including early progenitor cells. HPK1 is related distantly to the p21(Cdc42/Rac1)- activated kinase ( PAK) and yeast STE20 implicated in the mitogen-activated protein kinase ( MAPK) cascade. Expression of HPK1 activates JNK1 specifically, and it elevates strongly AP-1-mediated transcriptional activity in vivo. HPK1 binds and phosphorylates MEKK1 directly, whereas JNK1 activation by HPK1 is inhibited by a dominant-negative MEKK1 or MKK4/SEK mutant. Interestingly, unlike PAK65, HPK1 does not contain the small GTPase Rac1/ Cdc42- binding domain and does not bind to either Rac1 or Cdc42, suggesting that HPK1. activation is Rac1/ Cdc42-independent. These results indicate that HPK1 is a novel functional activator of the JNK/SAPK signaling pathway.[1]References
- Human HPK1, a novel human hematopoietic progenitor kinase that activates the JNK/SAPK kinase cascade. Hu, M.C., Qiu, W.R., Wang, X., Meyer, C.F., Tan, T.H. Genes Dev. (1996) [Pubmed]
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