title: DYNLL/LC8 protein controls signal transduction through the Nek9/Nek6 signaling module by regulating Nek6 binding to Nek9.
abstract: The NIMA family protein kinases Nek9/Nercc1 and the highly similar Nek6 and Nek7 form a signaling module activated in mitosis, when they are involved in the control of spindle organization and function. Here we report that Nek9, the module upstream kinase, binds to DYNLL/LC8, a highly conserved protein originally described as a component of the dynein complex. LC8 is a dimer that interacts with different proteins and has been suggested to act as a dimerization hub promoting the organization and oligomerization of partially disorganized partners. We find that the interaction of LC8 with Nek9 depends on a (K/R)XTQT motif adjacent to the Nek9 C-terminal coiled coil motif, results in Nek9 multimerization, and increases the rate of Nek9 autoactivation. LC8 binding to Nek9 is regulated by Nek9 activity through the autophosphorylation of Ser(944), a residue immediately N-terminal to the (K/R)XTQT motif. Remarkably, LC8 binding interferes with the interaction of Nek9 with its downstream partner Nek6 as well as with Nek6 activation, thus controlling both processes. Our work sheds light into the control of signal transduction through the module formed by Nek9 and Nek6/7 and uncovers a novel manner in which LC8 can regulate partner physiology by interfering with protein complex formation. We suggest that this and other LC8 functions can be specifically regulated by partner phosphorylation.
authors: Cell Signaling Group, Molecular Medicine Program, Institute for Research in Biomedicine (IRB Barcelona), 08028 Barcelona, Spain.
authors: Laura
authors: L
authors: Regué
authors: Sara
authors: S
authors: Sdelci
authors: M Teresa
authors: MT
authors: Bertran
authors: Carme
authors: C
authors: Caelles
authors: David
authors: D
authors: Reverter
authors: Joan
authors: J
authors: Roig
mesh_terms: D020816:Amino Acid Motifs; D056445:Cytoplasmic Dyneins / Q000235:genetics / Q000378:metabolism*; D004789:Enzyme Activation; D006801:Humans; D000072379:NIMA-Related Kinases; D010766:Phosphorylation; D017346:Protein Serine-Threonine Kinases / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction / Q000502:physiology*; D008941:Spindle Apparatus / Q000235:genetics / Q000378:metabolism
chemical_list: C459456:NEK6 protein, human; C462119:NEK9 protein, human; D000072379:NIMA-Related Kinases; D017346:Protein Serine-Threonine Kinases; C427758:DYNLL1 protein, human; D056445:Cytoplasmic Dyneins