Disease relevance of Melk

• We have isolated a cDNA clone of a new member of protein serine/threonine kinases, MPK38, from a cDNA library constructed from the murine teratocarcinoma PCC4 cell line by the polymerase chain reaction [1].

High impact information on Melk

• MELK expression in MNP is cell cycle regulated and inhibition of MELK expression down-regulates the expression of B-myb, which is shown to also mediate MNP proliferation [2].
• MELK down-regulation disrupts the production of neurogenic MNP from glial fibrillary acidic protein (GFAP)-positive progenitors in vitro [2].
• Here, we demonstrate expression of MELK by progenitors in developing and adult brain and that MELK serves as a marker for self-renewing multipotent neural progenitors (MNPs) in cultures derived from the developing forebrain and in transgenic mice [2].
• In adult mice, Melk was strongly expressed in the thymus and bone marrow, suggesting a role for Melk in hematopoiesis [3].
• Melk-like kinase plays a role in hematopoiesis in the zebra fish [3].

Biological context of Melk

• Given its expression pattern, Melk may play an important role during preimplantation embryonic development [4].
• As a basis for further study of the function of the gene, we have examined the expression of Melk across a wide range of embryonic stages, from the ovulated egg and 2-cell embryo through the gastrulation and early organogenesis stages, by in situ hybridization and immunohistochemistry [4].
• One of these, Melk, encodes a protein with a kinase catalytic domain and a leucine zipper motif, a new member of the Snf1/AMPK family of kinases [5].
• Thus, MPK38 gene product seems to play an important role in signal transduction of certain lineages of hematopoietic cells [1].
• Phosphorylation of a novel zinc-finger-like protein, ZPR9, by murine protein serine/threonine kinase 38 (MPK38) [6].

Anatomical context of Melk

• New member of the Snf1/AMPK kinase family, Melk, is expressed in the mouse egg and preimplantation embryo [5].
• A serine/threonine kinase, Melk, was initially cloned in mouse oocytes as a maternal gene, but whose function was unknown [3].
• We cloned a Melk-like gene from zebra fish (zMelk). zMelk-like gene was expressed in the brain and lateral mesoderm at 12 hours postfertilization (hpf) and in several tissues of adult fish, including the kidney and spleen, both of which are known to be hematopoietic tissues in zebra fish [3].
• An oligonucleotide microarray analysis of multiple human tumor samples and cell lines suggests that Melk expression is frequently elevated in cancer relative to normal tissues, a pattern confirmed by quantitative reverse transcription-PCR and Western blotting of selected primary tumor samples [7].
• To begin addressing whether Melk is relevant for tumorigenesis, RNA interference-mediated silencing within human and murine tumor cell lines was done [7].

Associations of Melk with chemical compounds

• N-terminus of MPK38 contains the kinase catalytic domain which exhibits approximately 60% protein sequence identity with the SNF1 serine/threonine kinase family [1].

Other interactions of Melk

• Repression of Cnap1 and Melk by 1,25(OH)(2)D(3) was confirmed not only in MC3T3-E1 cells but also in several other bone-unrelated cell types [8].
• The MPK38 cDNA directs the in vitro translation of two protein species of approx. 70 and approx. 50 kDa, which appear to result from an internal initiation of translation [1].
• These results suggest that MPK38 may play a functional role as one of the signal regulators in early T cell activation and, potentially, certain lineages of hematopoietic cell activation induced by Con A [9].

Analytical, diagnostic and therapeutic context of Melk

• We show that Melk knockdown decreases proliferation and anchorage-independent growth in vitro as well as tumor growth in a xenograft model [7].
• To understand the role of the MPK38 in thymocytes, we have investigated the level of MPK38 expression by Northern blot analysis [9].

References