|Application ||DB, E|
|Other Names||Mitogen-activated protein kinase kinase kinase kinase 1, Hematopoietic progenitor kinase, MAPK/ERK kinase kinase kinase 1, MEK kinase kinase 1, MEKKK 1, MAP4K1, HPK1|
|Target/Specificity||This MAP4K1 Antibody is generated from rabbits immunized with a KLH conjugated synthetic phosphopeptide corresponding to amino acid residues surrounding Y381 of human MAP4K1.|
|Format||Purified polyclonal antibody supplied in PBS with 0.09% (W/V) sodium azide. This antibody is first purified by protein A affinity chromatography. Then, the antibody fraction is peptide affinity purified in a 2-step procedure with peptides. The antibody is eluted with high and low pH buffers and neutralized immediately, followed by dialysis against PBS.|
|Storage||Maintain refrigerated at 2-8°C for up to 2 weeks. For long term storage store at -20°C in small aliquots to prevent freeze-thaw cycles.|
|Precautions||Phospho-MAP4K1(Y381) Antibody is for research use only and not for use in diagnostic or therapeutic procedures.|
|Function||Serine/threonine-protein kinase, which may play a role in the response to environmental stress. Appears to act upstream of the JUN N-terminal pathway. May play a role in hematopoietic lineage decisions and growth regulation. Able to autophosphorylate.|
|Tissue Location||Expressed primarily in hematopoietic organs, including bone marrow, spleen and thymus. Also expressed at very low levels in lung, kidney, mammary glands and small intestine|
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.
Hu M.C.-T., Genes Dev. 10:2251-2264(1996).
Beausoleil S.A., Proc. Natl. Acad. Sci. U.S.A. 101:12130-12135(2004).
Wissing J., Mol. Cell. Proteomics 6:537-547(2007).