Kinase Subfamily TESK

Kinase Classification: Group TKL: Family LISK: Subfamily TESK

The Testis Expressed Serine Kinases (TESKs) modulate the cytoskeleton in response to small GTPase signaling and have roles in axonal outgrowth and spermatogenesis.

Evolution

TESK is found across the metazoa (animals) but is lost in nematodes.

Domain Structure

TESKs have an N-terminal kinase domain and a similar length (~300 AA) of unannotated C-terminal region, often proline-rich

Functions

Despite the name, human TESK1 and TESK2 are expressed in several tissues outside of sperm (based on GTEx and Protein Atlas), and are believed to phosphorylate both serine/threonine and tyrosine [1].

LIMK kinases phosphorylate and inactivate the actin depolymerizing factor, cofilin. They are in turn activated by small GTPases such as Rho, Rac, and cdc42 which activate ROCK kinases, and also via PAKA and PAKB kinases. They have important roles in axon growth but appears to be active in many tissues.

The single Drosophila TESK, cdi (central divider) is expressed in the CNS midline [2] and required for axonal pathfinding [3], is required to maintain the actin cytoskeleton to enable sevenless signaling in the developing eye [4], and is downstream of Rac signaling in controlling Drosophila spermatogenesis [5]. It was also implicated in paxillin-Rho signaling in a wing genetic screen [6]. Both cdi and Drosophila LIMK were shown to enhance cofilin phosphorylation by cell line knockdown [7].

Rat TESK2 autophosphorylates on the activation loop at a residue (S215) that is conserved in all mouse, human and fly TESKs [1].

References

1. Toshima J, Tanaka T, and Mizuno K. Dual specificity protein kinase activity of testis-specific protein kinase 1 and its regulation by autophosphorylation of serine-215 within the activation loop. J Biol Chem. 1999 Apr 23;274(17):12171-6. DOI:10.1074/jbc.274.17.12171 |
2. Matthews BB and Crews ST. Drosophila center divider gene is expressed in CNS midline cells and encodes a developmentally regulated protein kinase orthologous to human TESK1. DNA Cell Biol. 1999 Jun;18(6):435-48. DOI:10.1089/104454999315150 |
3. Kraut R, Menon K, and Zinn K. A gain-of-function screen for genes controlling motor axon guidance and synaptogenesis in Drosophila. Curr Biol. 2001 Mar 20;11(6):417-30. DOI:10.1016/s0960-9822(01)00124-5 |
4. Sesé M, Corominas M, Stocker H, Heino TI, Hafen E, and Serras F. The Cdi/TESK1 kinase is required for Sevenless signaling and epithelial organization in the Drosophila eye. J Cell Sci. 2006 Dec 15;119(Pt 24):5047-56. DOI:10.1242/jcs.03294 |
5. Raymond K, Bergeret E, Avet-Rochex A, Griffin-Shea R, and Fauvarque MO. A screen for modifiers of RacGAP(84C) gain-of-function in the Drosophila eye revealed the LIM kinase Cdi/TESK1 as a downstream effector of Rac1 during spermatogenesis. J Cell Sci. 2004 Jun 1;117(Pt 13):2777-89. DOI:10.1242/jcs.01123 |
6. Chen GC, Turano B, Ruest PJ, Hagel M, Settleman J, and Thomas SM. Regulation of Rho and Rac signaling to the actin cytoskeleton by paxillin during Drosophila development. Mol Cell Biol. 2005 Feb;25(3):979-87. DOI:10.1128/MCB.25.3.979-987.2005 |
7. Dopie J, Rajakylä EK, Joensuu MS, Huet G, Ferrantelli E, Xie T, Jäälinoja H, Jokitalo E, and Vartiainen MK. Genome-wide RNAi screen for nuclear actin reveals a network of cofilin regulators. J Cell Sci. 2015 Jul 1;128(13):2388-400. DOI:10.1242/jcs.169441 |