Midkine

Midkine

Target · Growth factor

Midkine Midkine · Neurite growth-promoting factor 2

Midkine (MDK, also known as MK and NEGF2) is a secreted heparin-binding cytokine and growth factor of the pleiotrophin family. It signals through cell-surface proteoglycan and non-proteoglycan receptors to regulate cell growth, survival, migration and tissue repair. Browse Assay Genie's current range of Midkine research reagents below, or read on for the biology behind the target.

Secreted proteinCytokine and growth factorPleiotrophin family member
143 aa
Protein length
~16 kDa
Molecular weight
11p11.2
Gene locus
Pleiotrophin
Protein family
Target information

What is Midkine (midkine)?

Midkine is a secreted cytokine and growth factor that mediates its signal through cell-surface proteoglycan and non-proteoglycan receptors. It binds proteoglycan receptors via their chondroitin sulfate groups, and through these interactions it regulates inflammatory response, cell proliferation, adhesion, growth, survival, differentiation, migration and tissue regeneration. Reported binding partners include PTPRZ1, SDC3, GPC2, CSPG5, LRP1, the ITGA6:ITGB1 and ITGA4:ITGB1 integrin complexes, and anaplastic lymphoma kinase (ALK). ALK engagement leads to IRS1 phosphorylation and activation of MAPK and PI3-kinase signalling, driving cell proliferation. Midkine also promotes epithelial to mesenchymal transition through NOTCH2.

In inflammation, midkine recruits neutrophils and macrophages, both directly (cooperating with ITGB2 via LRP1) and by inducing chemokine expression. It also suppresses tolerogenic dendritic cells, which limits regulatory T cell differentiation, and promotes T cell expansion through NFAT signalling and Th1 differentiation. After injury it supports regeneration of the heart, liver and bone, promotes cell survival through MAPK and AKT pathways, and during arteriogenesis induces VEGFA expression. In bone it negatively regulates formation in response to mechanical load by inhibiting Wnt/beta-catenin signalling in osteoblasts. In the brain it promotes survival and growth of neural precursor cells, neuronal migration and neurite outgrowth, and it has been linked to hippocampal development and working memory.

The MDK gene encodes a member of a small family of secreted growth factors that binds heparin and responds to retinoic acid. Alternatively spliced transcript variants encoding multiple isoforms have been observed. Midkine was previously named neurite growth-promoting factor 2 (NEGF2). RefSeq notes that it promotes cell growth, migration and angiogenesis, particularly during tumorigenesis, and the gene has been targeted as a therapeutic for a variety of disorders. Mouse and rat both carry an ortholog named Mdk.

Inflammation and immunology

Midkine recruits neutrophils and macrophages and shapes T cell and dendritic cell responses, making it relevant to inflammatory signalling.

Tissue repair and regeneration

Midkine promotes cell survival and regeneration after heart, liver and bone injury, and supports chondrocyte differentiation.

Neuroscience and development

Midkine supports neural precursor survival, neuronal migration and neurite outgrowth, and is linked to hippocampal development.

Cancer and angiogenesis

Midkine promotes cell growth, migration and angiogenesis, particularly during tumorigenesis, and has been explored as a therapeutic target.

Background

Midkine frequently asked questions

What does midkine do?

Midkine is a secreted cytokine and growth factor. It signals through proteoglycan and non-proteoglycan receptors to regulate cell proliferation, survival, adhesion and migration, and it contributes to inflammation, tissue regeneration, angiogenesis and neural development. Check the datasheet of any product for its validated reactivity.

What other names does midkine go by?

The gene symbol is MDK. Aliases include MK, FLJ27379 and NEGF2, and the previous name was neurite growth-promoting factor 2. RefSeq reports that alternatively spliced transcript variants encode multiple isoforms of the protein.

Which family does midkine belong to, and is it conserved?

Midkine belongs to the pleiotrophin family, a small group of secreted, heparin-binding growth factors. Orthologs named Mdk exist in mouse and rat. Human MDK has also been linked to tumorigenesis through its roles in cell growth, migration and angiogenesis.

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Related targets

Pleiotrophin family members, midkine receptors and signalling partners that are linked to growth, inflammation and angiogenesis.

Gene and protein annotations from HGNC, NCBI Gene and UniProt P21741; product specifications from Assay Genie datasheets.

Midkine Product listing