Protein function and interaction

TTK is a serine/threonine and tyrosine protein kinase that acts as a regulator of the mitotic spindle-assembly checkpoint (Stucke et al., 2002 PMID: 11927556; Liu et al., 2003 PMID: 12686615) and also controls the correction of improper chromosome attachments, through a direct interaction and phosphorylation of borealin and regulation of Aurora B kinase activity (Jelluma et al., 2008 PMID: 18243099). Mps1 is required, together with Hec1 protein, for recruiting the Mad1/Mad2 complex to kinetochores.(Martin-Lluesma et al., 2002 PMID: 12351790) and Mps1 catalytic activity is required for spindle checkpoint function and for the kinetochore localization of Mad2 (Tighe et al., 2008 PMID: 18541701). The centrosomal protein TACC2 is phosphorylated in mitosis by TTK (Dou et al., 2004 PMID: 15304323). The heat shock protein mortalin binds to Mps1, and is phosphorylated by Mps1. (Kanai et al., 2007 PMID: 17573779). MPS1 (TTK) interacts with BLM helicase (Bloom syndrome gene) that is phosphorylated in a MPS1-dependent manner (Leng et al., 2006 PMID: 1686479).

Human Mps1 (TTK) might play a role in centrosome duplication (Fisk et al., 2003 PMID: 14657364).

A yeast two-hybrid screen showed that TTK/hMps1 directly phosphorylates CHK2, that plays important roles in the DNA damage-induced cell cycle checkpoint, suggesting a possible cross-talk between the spindle assembly checkpoint and the DNA damage checkpoint (Wei et al., 2005 PMID: 1561822). TTK also phosphorylates c-Abl upon exposure to genotoxic stress (Nikira et al., 2008 PMID: 18794806). TTK (hMPS1) may be involved in DNA damaged/p53 induced apoptosis (Bhonde et al., 2006 PMID: 16446370).