A functional cooperativity between Aurora A kinase and LIM kinase1: implication in the mitotic process.
Aurora kinase A (Aur-A), a mitotic kinase, regulates initiation of mitosis through centrosome separation and proper assembly of bipolar spindles. LIM kinase 1 (LIMK1), a modulator of actin and microtubule dynamics, is involved in the mitotic process through inactivating phosphorylation of cofilin. Phosphorylated LIMK1 is recruited to the centrosomes during early prophase, where it colocalizes with γ-tubulin. Here, we report a novel functional cooperativity between Aur-A and LIMK1 through mutual phosphorylation. LIMK1 is recruited to the centrosomes during early prophase and then to the spindle poles, where it colocalizes with Aur-A. Aur-A physically associates with LIMK1 and activates it through phosphorylation, which is important for its centrosomal and spindle pole localization. Aur-A also acts as a substrate of LIMK1, and the function of LIMK1 is important for its specific localization and regulation of spindle morphology. Taken together, the novel molecular interaction between these two kinases and their regulatory roles on one another's function may provide new insight on the role of Aur-A in manipulation of actin and microtubular structures during spindle formation.
Burnett School of Biomedical Sciences, College of Medicine, University of Central Florida, Orlando, FL, USA.
Lisa
L
Ritchey
Richard
R
Ottman
Michael
M
Roumanos
Ratna
R
Chakrabarti
D064096:Aurora Kinase A; D064127:Aurora Kinases; D002460:Cell Line; D018385:Centrosome / Q000378:metabolism; D006801:Humans; D054461:Lim Kinases / Q000378:metabolism*; D008856:Microscopy, Fluorescence; D008938:Mitosis; D010766:Phosphorylation; D010768:Phosphoserine / Q000378:metabolism; D011485:Protein Binding; D054730:Protein Interaction Domains and Motifs; D011499:Protein Processing, Post-Translational; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism*; D021381:Protein Transport; D008941:Spindle Apparatus / Q000378:metabolism*
D010768:Phosphoserine; C576917:AURKA protein, human; D064096:Aurora Kinase A; D064127:Aurora Kinases; C515892:LIMK1 protein, human; D054461:Lim Kinases; D017346:Protein Serine-Threonine Kinases