Difference between revisions of "Kinase Subfamily MAK"

From WikiKinome
Jump to: navigation, search
 
m
 
(9 intermediate revisions by one user not shown)
Line 8: Line 8:
  
 
====Activation====
 
====Activation====
All MAK kinases have a TEY motif in their activation loop. The Y is autophosphorylated, while the T is phosphorylated by [[Kinase_Subfamily_CDK20|CDK20]] (CCRK) <cite>Fu</cite>. Protein phosphatase 5 (PP5) binds to and can dephosphorylate ICK on T157
+
Most MAK kinases have a T[DE]Y motif in their [[activation loop]]. In ICK, the Y159 is autophosphorylated, and required for basal activity, while the T is transphosphorylated. In vitro, ICK can be threonine-phosphorylated by [[Kinase_Subfamily_CDK20|CDK20]] (CCRK) <cite>Fu</cite>, or by CAK1 (CDK-activating kinase) but not by human CDK7, MEK1 or MEK5<cite>Fu2</cite>. Protein phosphatase 5 (PP5) binds to and can dephosphorylate ICK on T157. Thus the activation loop looks like MAPK in terms of the TxY, but possibly like a CDK in terms of CAK1 activation. By contrast, a MAK from the fungus Ustilago maydis is apparently activated by a MEK1 kinase <cite>Garrido</cite>
  
 
====Function====
 
====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.
+
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 <cite>Bladt</cite>. 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 <cite>Omori</cite>. [http://biogps.org 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.
  
Yeast IME2 is involved in meiosis and pseudohyphal growth
+
MAK knockout mice <cite>Shinkai</cite> have no major abnormalities, though they have slightly reduced litter sizes and sperm motility.
  
Human ICK (Intestinal Cell Kinase)
+
Knockdown of ICK in intestinal epithelial cells inhibited cell cycle progress, and also protein translation, though a likely binding and phosphorylation of the mTOR-Raptor complex <cite>Fu3</cite>. A hypomorphic mutation in ICK causes endocrine-cerebro-osteodysplasia (ECO), a neonatal-lethal disease with multiple disorders in skeletal, cerebral, genital, pituitary and endocrine development <cite>Lahiry</cite>. The phenotypes are similar to those of Majewski syndrome, which may be caused by the NEK1 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 <cite>Bladt</cite>. 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 <cite>Omori</cite>
+
ICK has two splice forms, of which the longer is cytoplasmic and the shorter is nuclear <cite>Fu2</cite>. Despite its name ICK is expressed in many tissues, and
  
MAK binds and activates Androgen Receptor (AR) in prostate cell lines <cite>Ma</cite>. In turn, AR induces expression of the MAK promoter <cite>Xia</cite>
+
Loss of function mutants of MAK in Chlamydomonas <cite>Berman</cite>, C. elegans <cite></cite>, and Leishmania <cite>Bengs</cite> result in abnormally long cilia, while overexpression leads to truncated cilia.
 
+
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]
+
  
 +
C. elegans dyf-5 (M04C9.5) is well-characterized for its 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 <cite>Chen</cite>. It is expressed in several sets of ciliated chemosensory neurons and male-specific cells, and required for normal chemotaxis, dauer formation, and male mating <cite>Starich</cite>. dyf-5 may be involved in docking and undocking of cargo from two distinct kinesin motors within the cilium <cite>Burghoon</cite>.
  
 +
Yeast IME2 is involved in meiosis and pseudohyphal growth <cite>Strudwick</cite>. Schizosaccharomyces pombe has two MAK genes, Mde3 and Pit1, which interact genetically and are regulated by the meiosis-specific transcription factor, Mei4<cite>Abe</cite>; mutants have minor defects in sporulation. Other fungal MAK genes have roles in mating and fruiting body formation (reviewed in <cite>Irniger</cite>).
  
 
===References===
 
===References===
 
<biblio>
 
<biblio>
 +
# Abe pmid=10747048
 +
# Bengs pmid=15720564
 +
# Berman pmid=12842015
 +
# Burghoorn pmid=17420466
 
# Bladt pmid=8359591
 
# Bladt pmid=8359591
 +
# Chen pmid=17187676
 
# Fu pmid=16954377
 
# Fu pmid=16954377
 +
# Fu2 pmid=15988018
 +
# Fu3 pmid=19696144
 +
# Irniger pmid=21306447
 +
# Lahiry pmid=19185282
 
# Ma pmid=16951154
 
# Ma pmid=16951154
 
# Omori pmid=21148103
 
# Omori pmid=21148103
 +
# Shinkai pmid=11971961
 +
# Starich pmid=7705621
 
# Xia pmid=12084720
 
# Xia pmid=12084720
 +
# Garrido pmid=15601825
 +
# Strudwick pmid=20876298
 
</biblio>
 
</biblio>

Latest revision as of 20:02, 2 May 2014

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

Most MAK kinases have a T[DE]Y motif in their activation loop. In ICK, the Y159 is autophosphorylated, and required for basal activity, while the T is transphosphorylated. In vitro, ICK can be threonine-phosphorylated by CDK20 (CCRK) [1], or by CAK1 (CDK-activating kinase) but not by human CDK7, MEK1 or MEK5[2]. Protein phosphatase 5 (PP5) binds to and can dephosphorylate ICK on T157. Thus the activation loop looks like MAPK in terms of the TxY, but possibly like a CDK in terms of CAK1 activation. By contrast, a MAK from the fungus Ustilago maydis is apparently activated by a MEK1 kinase [3]

Function

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 [4]. 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 [5]. 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 (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 [6] have no major abnormalities, though they have slightly reduced litter sizes and sperm motility.

Knockdown of ICK in intestinal epithelial cells inhibited cell cycle progress, and also protein translation, though a likely binding and phosphorylation of the mTOR-Raptor complex [7]. A hypomorphic mutation in ICK causes endocrine-cerebro-osteodysplasia (ECO), a neonatal-lethal disease with multiple disorders in skeletal, cerebral, genital, pituitary and endocrine development [8]. The phenotypes are similar to those of Majewski syndrome, which may be caused by the NEK1 kinase.

ICK has two splice forms, of which the longer is cytoplasmic and the shorter is nuclear [2]. Despite its name ICK is expressed in many tissues, and

Loss of function mutants of MAK in Chlamydomonas [9], C. elegans [], and Leishmania [10] result in abnormally long cilia, while overexpression leads to truncated cilia.

C. elegans dyf-5 (M04C9.5) is well-characterized for its 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 [11]. It is expressed in several sets of ciliated chemosensory neurons and male-specific cells, and required for normal chemotaxis, dauer formation, and male mating [12]. dyf-5 may be involved in docking and undocking of cargo from two distinct kinesin motors within the cilium [13].

Yeast IME2 is involved in meiosis and pseudohyphal growth [14]. Schizosaccharomyces pombe has two MAK genes, Mde3 and Pit1, which interact genetically and are regulated by the meiosis-specific transcription factor, Mei4[15]; mutants have minor defects in sporulation. Other fungal MAK genes have roles in mating and fruiting body formation (reviewed in [16]).

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. Fu Z, Schroeder MJ, Shabanowitz J, Kaldis P, Togawa K, Rustgi AK, Hunt DF, and Sturgill TW. Activation of a nuclear Cdc2-related kinase within a mitogen-activated protein kinase-like TDY motif by autophosphorylation and cyclin-dependent protein kinase-activating kinase. Mol Cell Biol. 2005 Jul;25(14):6047-64. DOI:10.1128/MCB.25.14.6047-6064.2005 | PubMed ID:15988018 | HubMed [Fu2]
  3. Garrido E, Voss U, Müller P, Castillo-Lluva S, Kahmann R, and Pérez-Martín J. The induction of sexual development and virulence in the smut fungus Ustilago maydis depends on Crk1, a novel MAPK protein. Genes Dev. 2004 Dec 15;18(24):3117-30. DOI:10.1101/gad.314904 | PubMed ID:15601825 | HubMed [Garrido]
  4. 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]
  5. 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]
  6. 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]
  7. Fu Z, Kim J, Vidrich A, Sturgill TW, and Cohn SM. Intestinal cell kinase, a MAP kinase-related kinase, regulates proliferation and G1 cell cycle progression of intestinal epithelial cells. Am J Physiol Gastrointest Liver Physiol. 2009 Oct;297(4):G632-40. DOI:10.1152/ajpgi.00066.2009 | PubMed ID:19696144 | HubMed [Fu3]
  8. Lahiry P, Wang J, Robinson JF, Turowec JP, Litchfield DW, Lanktree MB, Gloor GB, Puffenberger EG, Strauss KA, Martens MB, Ramsay DA, Rupar CA, Siu V, and Hegele RA. A multiplex human syndrome implicates a key role for intestinal cell kinase in development of central nervous, skeletal, and endocrine systems. Am J Hum Genet. 2009 Feb;84(2):134-47. DOI:10.1016/j.ajhg.2008.12.017 | PubMed ID:19185282 | HubMed [Lahiry]
  9. Berman SA, Wilson NF, Haas NA, and Lefebvre PA. A novel MAP kinase regulates flagellar length in Chlamydomonas. Curr Biol. 2003 Jul 1;13(13):1145-9. DOI:10.1016/s0960-9822(03)00415-9 | PubMed ID:12842015 | HubMed [Berman]
  10. Bengs F, Scholz A, Kuhn D, and Wiese M. LmxMPK9, a mitogen-activated protein kinase homologue affects flagellar length in Leishmania mexicana. Mol Microbiol. 2005 Mar;55(5):1606-15. DOI:10.1111/j.1365-2958.2005.04498.x | PubMed ID:15720564 | HubMed [Bengs]
  11. Chen N, Mah A, Blacque OE, Chu J, Phgora K, Bakhoum MW, Newbury CR, Khattra J, Chan S, Go A, Efimenko E, Johnsen R, Phirke P, Swoboda P, Marra M, Moerman DG, Leroux MR, Baillie DL, and Stein LD. Identification of ciliary and ciliopathy genes in Caenorhabditis elegans through comparative genomics. Genome Biol. 2006;7(12):R126. DOI:10.1186/gb-2006-7-12-r126 | PubMed ID:17187676 | HubMed [Chen]
  12. Starich TA, Herman RK, Kari CK, Yeh WH, Schackwitz WS, Schuyler MW, Collet J, Thomas JH, and Riddle DL. Mutations affecting the chemosensory neurons of Caenorhabditis elegans. Genetics. 1995 Jan;139(1):171-88. PubMed ID:7705621 | HubMed [Starich]
  13. Strudwick N, Brown M, Parmar VM, and Schröder M. Ime1 and Ime2 are required for pseudohyphal growth of Saccharomyces cerevisiae on nonfermentable carbon sources. Mol Cell Biol. 2010 Dec;30(23):5514-30. DOI:10.1128/MCB.00390-10 | PubMed ID:20876298 | HubMed [Strudwick]
  14. Abe H and Shimoda C. Autoregulated expression of Schizosaccharomyces pombe meiosis-specific transcription factor Mei4 and a genome-wide search for its target genes. Genetics. 2000 Apr;154(4):1497-508. PubMed ID:10747048 | HubMed [Abe]
  15. Irniger S. The Ime2 protein kinase family in fungi: more duties than just meiosis. Mol Microbiol. 2011 Apr;80(1):1-13. DOI:10.1111/j.1365-2958.2011.07575.x | PubMed ID:21306447 | HubMed [Irniger]
  16. Burghoorn J, Dekkers MP, Rademakers S, de Jong T, Willemsen R, and Jansen G. Mutation of the MAP kinase DYF-5 affects docking and undocking of kinesin-2 motors and reduces their speed in the cilia of Caenorhabditis elegans. Proc Natl Acad Sci U S A. 2007 Apr 24;104(17):7157-62. DOI:10.1073/pnas.0606974104 | PubMed ID:17420466 | HubMed [Burghoorn]
  17. 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]
  18. 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