LIM kinases directly phosphorylate and inactivate members of the cofilin family, resulting in stabilization of filamentous (F)-actin.
[4] LIM kinase family proteins regulate actin polymerization through the phosphorylation of cofilin at Ser-3, inactivating its actin-depolymerizing activity.
[7] As a result, the LIM kinases are hypothesized to take part in a checkpoint for aberrant spindle assembly due to external stress.
[8] LIMK1 has been found to localize to cell-cell adhesion sites during interphase and prophase, the spindle poles during prometaphase and anaphase, and the contractile ring during telophase.
LIMK2 deficiency leads to abnormal mitotic spindle formation, thought the exact molecular mechanism by which this occurs and how LIMK2 regulates mitosis remains unknown.
The presence of multiple splice variants makes it particularly difficult to full determine LIM kinase expression patterns.
LIM kinases serve as downstream effectors within the non-canonical nerve growth factor, semaphoric, and bone morphogenic protein (BMP) pathways.
BMP type-2 receptors (BMPRII) contain a 600 amino acid long cytoplasmic domain that is capable of interacting with and suppressing the activation of LIMK1 by PAK.
Knock out experiments in both mice and Drosophila melanogaster suggest that LIMK1 plays a significant role in neuron differentiation and normal synaptic development, particularly in neuromuscular and olfactory synapses.
[26] Inhibition of LIMK1 in mice during capacitation resulted in decreased actin polymerization and a severe reduction in the percentage of sperm that underwent acrosomal exocytosis.
Overexpression of LIMK1 in particular has been associated with heightened risk of metastasis, leading to it being considered as a potential drug target to reduce cancer motility.