| Human enhancer of filamentation protein 1 (HEF1), also known as neural precursor cell expressed developmentally down-regulated protein 9 (NEDD9), is part of the Cas family of proteins, which include HEF1/NEDD9, p130Cas and Efs. HEF1 is a predominantly cytoplasmic protein, localizing to focal adhesions during interphase, and centrosomes and other parts of the mitotic apparatus during G2/M phase of the cell cycle. HEF1 is a docking protein that plays a central coordinating role for tyrosine kinase-based signaling related to cell adhesion, motility, growth and apoptosis. Phosphorylation of HEF1 is induced by a number of factors, including FAK, TGF-β, PDGFR, Abl, and BCR-ABL, which leads to coordinate binding of multiple downstream effector proteins via 15 known SH2 domain-binding sites. HEF1 is a key regulator of cancer metastasis. It is required for the invasive activity of glioblastomas, is linked to the promotion of metastasis in melanoma, and is found to be up-regulated in lung cancer metastasis. |
