Midkine (MK, also called neurite growth promoting factor 2, NEGF-2), a product of a retinoic acid responsive gene, is a secreted 13 kDa protein belonging to the family of heparin binding growth/differentiation factors. MK shares 45% sequence identity with other member of this family called Pleiotrophin (HB-GAM). Midkine is composed of two domains held together by disulfide linkages. The C-terminally located domain contains two heparin binding sites and is usually responsible for midkine activity. Part of the MK activity is enhanced by dimerization of MK.
Midkine has been found in vertebrates from human to zebrafish and is most strongly expresed in midgestation. In the adult MK expression is restricted. In addition to normal development, MK is also involved in the pathogenesis of diseases e.g. inflammatory diseases, human carcinomas such as esophageal, stomach, colon, pancreatic, thyroid, lung, urinary, hepatocellular, neuroblastoma, glioblastoma, Wilm´s tumor etc. High MK levels are associated with poor prognosis in some type of cancer. The increased expresion in many carcinomas indicates that MK can be applied to the diagnosis of malignancy. Midkine is expressed during the reparative stage of bone fractures, also supresses infection of certain viruses including HIV in target cells. Anti-apoptotic and cell protecting activity of midkine makes it to be a promissing in therapy.
Areas of investigation: Oncology, Inflammatory diseases, Preservation and repair of injured tissues.
- References to Midkine (MK, NEGF-2, Neurite growth promoting factor 2)