TNIK
Traf2 and NcK interacting kinase (TNIK; EC 2.7.11.1) is a protein with both scaffolding and kinase domains that had been implicated in postsynaptic signalling (glutamate receptor regulation in vitro) as well as in regulation of cell proliferation. As a member of the germinal centre kinase family, TNIK can activate the c-Jun N-terminal kinase pathway similar to many GCKs. Moreover, the protein has been implicated in Wnt signaling, as it interacts with TCF4 in the proliferative crypts of mouse small intestine, functioning as a transcriptional activator to promoters of Wnt target genes in a β-catenin-dependent manner[1]. As such, TNIK also seems to be an important factor in the growth of colorectal cancer cells[2]. In the nervous system, phosphorylation of TNIK seems to be regulated by the activation of NMDA receptors, and it has also been implicated in controlling dendritic outgrowth mediated by a ternary complex involving the E3 ubiquitin ligase Nedd4-1, Rap2A and TNiK. Therefore, the kinase could also play a role in cognitive functions through both synaptic and nuclear signalling pathways[3].
[1] T. Mahmoudi et al. The kinase TNIK is an essential activator of Wnt target genes. EMBO J. 2009 Nov 4;28(21):3329-40.
[2] M. Shitashige et al. Traf2- and Nck-interacting kinase is essential for Wnt signaling and colorectal cancer growth. Cancer Res 2010; 70: 5024–5033.
[3] M.P. Coba et al. TNiK is required for postsynaptic and nuclear signaling pathways and cognitive function. J Neurosci. 2012 Oct 3;32(40):13987-99.