MAP4K1
Function
Serine/threonine-protein kinase, which plays a role in the response to environmental stress (PubMed:24362026). Appears to act upstream of the JUN N-terminal pathway (PubMed:8824585). Activator of the Hippo signaling pathway which plays a pivotal role in organ size control and tumor suppression by restricting proliferation and promoting apoptosis. MAP4Ks act in parallel to and are partially redundant with STK3/MST2 and STK4/MST2 in the phosphorylation and activation of LATS1/2, and establish MAP4Ks as components of the expanded Hippo pathway (PubMed:26437443). May play a role in hematopoietic lineage decisions and growth regulation (PubMed:24362026, PubMed:8824585). Together with CLNK, it enhances CD3-triggered activation of T-cells and subsequent IL2 production (By similarity).
Post-translational modifications
Autophosphorylates: phosphorylation promotes ubiquitination by the Cul7-RING(FBXW8) ubiquitin-protein ligase complex, leading to its degradation by the proteasome.
Tyrosine-phosphorylated after activation of hemopoietic cells.
Ubiquitinated by the Cul7-RING(FBXW8) ubiquitin-protein ligase complex following autophosphorylation, leading to its degradation by the proteasome.
Sequence Similarities
Belongs to the protein kinase superfamily. STE Ser/Thr protein kinase family. STE20 subfamily.
Tissue Specificity
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.
Alternative names
HPK1, MAP4K1, Mitogen-activated protein kinase kinase kinase kinase 1, Hematopoietic progenitor kinase, MAPK/ERK kinase kinase kinase 1, MEK kinase kinase 1, MEKKK 1