Kinase Subfamily MAK

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Kinase Classification: Group CMGC: Family RCK: MAK

Evolution

MAK is found in all eukaryotes examined to date. Vertebrates have two copies: MAK and ICK, while most invertebrates have one copy.

Domain Structure

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

Activation

All MAK kinases have a TEY motif in their activation loop. The Y is autophosphorylated, while the T is phosphorylated by CDK20 (CCRK) [1]. Protein phosphatase 5 (PP5) binds to and can dephosphorylate ICK on T157

Function

C. elegans dyf-5 (M04C9.5) is well-characterized for it's role in regulating flagellar length, and the localization of several other proteins in the flagellum (cilium). Dyf-5 is expressed under the control of the flagellar transcription factor, DAF-19.

Yeast IME2 is involved in meiosis and pseudohyphal growth.

Human ICK (Intestinal Cell Kinase)

Human MAK (Male germ-cell Associated Kinase) is expressed almost exclusively in germ cells of the testis. In rodents, it associates with the synaptonemal complex (paired chromosomes) during meiosis. Mouse MAK is also expressed in developing sensory epithelia, including photoreceptors, olfactory receptors and the respiratory tract [2]. In the retina, MAK is found in the connecting cilia and outer-segment axonemes of photoreceptor cells and loss of MAK results in longer cilia [3]. BioGPS data show human and mouse MAK highly restricted to retina, pineal gland, testis, olfactory epithelium and possibly lung in adult tissues, while ICK is more broadly expressed, though elevated in lung, retina and intestine. Antibody staining ([http://proteinatlas.org proteinatlas.org) shows ICK in cytoplasmic vesicles (possibly golgi or mitochondria) and in tissues, found in gastro-intestinal tract, nasopharynx and cervix. MAK was found weakly in the cytoplasm and also in the nucleus, with strongest staining in stomach and Purkinje cells.

MAK knockout mice [4] have no major abnormalities, though they have slighly reduced litter sizes and sperm motility.


Other homologs include Mde3 and Pit1 in Schizosaccharomyces pombe .

dyf-5 encodes a putative MAP kinase orthologous to human MAK/ICK (OMIM:154235), Chlamydomonas reinhardtii LF4, and Leishmania mexicana MPK9; DYF-5 negatively regulates cilial length, restricts KAP-1 to middle ciliary segments, is required for normal localization of six IFT components, and is required for OSM-3 to comigrate normally with IFT particles; DYF-5 is also required for dye-filling of amphid and phasmid neurons and for normal chemotaxis, dauer formation, and male mating; DYF-5 is expressed in head neurons (including amphid neurons), tail neurons (including phasmid neurons), CAN cells, excretory canal neurons, posterior lateral ganglion neurons and in many male tail cells; dyf-5 mutant cilia are abnormally elongated, either failing to enter the amphid channel or accumulating IFT proteins at their distal ends, whereas DYF-5 overexpression results in truncated cilia; the dyf-5 promoter region contains an X-box, predicted to be bound and transcriptionally activated by DAF-19, and dyf-5 is regulated by DAF-19 in vivo; dyf-5 animals are slightly shorter than normal. [details]


References

  1. Fu Z, Larson KA, Chitta RK, Parker SA, Turk BE, Lawrence MW, Kaldis P, Galaktionov K, Cohn SM, Shabanowitz J, Hunt DF, and Sturgill TW. Identification of yin-yang regulators and a phosphorylation consensus for male germ cell-associated kinase (MAK)-related kinase. Mol Cell Biol. 2006 Nov;26(22):8639-54. DOI:10.1128/MCB.00816-06 | PubMed ID:16954377 | HubMed [Fu]
  2. Bladt F and Birchmeier C. Characterization and expression analysis of the murine rck gene: a protein kinase with a potential function in sensory cells. Differentiation. 1993 Jun;53(2):115-22. DOI:10.1111/j.1432-0436.1993.tb00651.x | PubMed ID:8359591 | HubMed [Bladt]
  3. Omori Y, Chaya T, Katoh K, Kajimura N, Sato S, Muraoka K, Ueno S, Koyasu T, Kondo M, and Furukawa T. Negative regulation of ciliary length by ciliary male germ cell-associated kinase (Mak) is required for retinal photoreceptor survival. Proc Natl Acad Sci U S A. 2010 Dec 28;107(52):22671-6. DOI:10.1073/pnas.1009437108 | PubMed ID:21148103 | HubMed [Omori]
  4. Shinkai Y, Satoh H, Takeda N, Fukuda M, Chiba E, Kato T, Kuramochi T, and Araki Y. A testicular germ cell-associated serine-threonine kinase, MAK, is dispensable for sperm formation. Mol Cell Biol. 2002 May;22(10):3276-80. DOI:10.1128/mcb.22.10.3276-3280.2002 | PubMed ID:11971961 | HubMed [Shinkai]
  5. Ma AH, Xia L, Desai SJ, Boucher DL, Guan Y, Shih HM, Shi XB, deVere White RW, Chen HW, Tepper CG, and Kung HJ. Male germ cell-associated kinase, a male-specific kinase regulated by androgen, is a coactivator of androgen receptor in prostate cancer cells. Cancer Res. 2006 Sep 1;66(17):8439-47. DOI:10.1158/0008-5472.CAN-06-1636 | PubMed ID:16951154 | HubMed [Ma]
  6. Xia L, Robinson D, Ma AH, Chen HC, Wu F, Qiu Y, and Kung HJ. Identification of human male germ cell-associated kinase, a kinase transcriptionally activated by androgen in prostate cancer cells. J Biol Chem. 2002 Sep 20;277(38):35422-33. DOI:10.1074/jbc.M203940200 | PubMed ID:12084720 | HubMed [Xia]
All Medline abstracts: PubMed | HubMed