Kinase Subfamily MOK

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Kinase Classification: Group CMGC: Family RCK: MOK

Evolution

MOK is a primordial eukaryotic kinase, predicted to be in the last common ancestor of all eukaryotes. However, it has been lost from several lineages, including nematodes, insects, fungi, and higher plants. The single human member is called MOK (MAPK/MAK/MRK Overlapping Kinase), also known as RAGE1 (renal tumor antigen).

Domain Structure

All MOK kinases have an N-terminal kinase domain and a variable length (~100-300 AA) C-terminal tail without any known domains.

Function

MOK function is poorly understood. Its absence from organisms that have also lost motile cilia, and the association of the related MAK kinases to cilia suggests that it might be involved in motile cilia function. This is supported by LF4, the Chlamydomonas MOK. LF4 regulates flagellum growth and interacts genetically with LF2 (a CDK20 subfamily kinase) [1].

Human MOK transcript is expressed in testis, thyroid, retina, while mouse is largely expressed in testis and maybe in two stem cell lines BioGPS. Mouse MOK is selectively expressed in intestinal crypt cells, under the regulation of the Cdx2 homeodomain protein [2]. The mouse gene was also reported as expressed mostly in testicular germ cells (Gopalan et al - no Medline citation but the direct link is http://onlinelibrary.wiley.com/doi/10.1002/(SICI)1098-2795(199901)52:1%3C9::AID-MRD2%3E3.0.CO;2-O/citedby ). Human MOK protein is localized to the cytoplasm and stained the Golgi in one cell line (http://proteinatlas.org).

Human MOK specifically associates with the chaperones Hsp90 and Cdc37 [3]; phosphorylation of Cdc37 by CK2 was required for this association [4].

MOK is also known as RAGE1 (Renal Tumor Antigen), as a tumor-associated antigen that is recognized by autologous cytolytic T cells [5]. RAGE1 was isolated from a renal cell carcinoma, but was not expressed in other RCC samples, though it was reported in normal retina and in a variety of other tumors (e.g. [6, 7, 8]).

References

  1. Uesaka T and Kageyama N. Cdx2 homeodomain protein regulates the expression of MOK, a member of the mitogen-activated protein kinase superfamily, in the intestinal epithelial cells. FEBS Lett. 2004 Aug 27;573(1-3):147-54. DOI:10.1016/j.febslet.2004.07.070 | PubMed ID:15327990 | HubMed [Uesaka]
  2. Miyata Y, Ikawa Y, Shibuya M, and Nishida E. Specific association of a set of molecular chaperones including HSP90 and Cdc37 with MOK, a member of the mitogen-activated protein kinase superfamily. J Biol Chem. 2001 Jun 15;276(24):21841-8. DOI:10.1074/jbc.M010944200 | PubMed ID:11278794 | HubMed [Miyata2]
  3. Miyata Y and Nishida E. CK2 controls multiple protein kinases by phosphorylating a kinase-targeting molecular chaperone, Cdc37. Mol Cell Biol. 2004 May;24(9):4065-74. PubMed ID:15082798 | HubMed [Miyata]
  4. Gaugler B, Brouwenstijn N, Vantomme V, Szikora JP, Van der Spek CW, Patard JJ, Boon T, Schrier P, and Van den Eynde BJ. A new gene coding for an antigen recognized by autologous cytolytic T lymphocytes on a human renal carcinoma. Immunogenetics. 1996;44(5):323-30. PubMed ID:8781117 | HubMed [Gaugler]
  5. Guinn BA, Gilkes AF, Mufti GJ, Burnett AK, and Mills KI. The tumour antigens RAGE-1 and MGEA6 are expressed more frequently in the less lineage restricted subgroups of presentation acute myeloid leukaemia. Br J Haematol. 2006 Jul;134(2):238-9. DOI:10.1111/j.1365-2141.2006.06135.x | PubMed ID:16846483 | HubMed [Guinn]
  6. Neumann E, Engelsberg A, Decker J, Störkel S, Jaeger E, Huber C, and Seliger B. Heterogeneous expression of the tumor-associated antigens RAGE-1, PRAME, and glycoprotein 75 in human renal cell carcinoma: candidates for T-cell-based immunotherapies?. Cancer Res. 1998 Sep 15;58(18):4090-5. PubMed ID:9751617 | HubMed [Neumann]
  7. Eichmüller S, Usener D, Jochim A, and Schadendorf D. mRNA expression of tumor-associated antigens in melanoma tissues and cell lines. Exp Dermatol. 2002 Aug;11(4):292-301. PubMed ID:12190937 | HubMed [Eichmuller]
All Medline abstracts: PubMed | HubMed