Misshapen/NIKs-related
kinase (MINK) is a member of the germinal center family of
kinases that are homologous to the yeast sterile 20 (Ste20)
kinases and regulate a wide variety of cellular processes, including cell morphology, cytoskeletal rearrangement, and survival. Here, we present the cloning and functional characterization of a novel human Misshapen/NIKs-related
kinase beta (hMINK beta) that encodes a
polypeptide of 1312
amino acids. hMINK beta is ubiquitously expressed in most tissues with at least five alternatively spliced
isoforms. Similar to Nck interacting
kinase (NIK) and
Traf2 and Nck-interacting
kinase (TNIK), hMINK beta moderately activates
c-Jun N-terminal kinase (JNK) and associates with Nck via the intermediate domain in the yeast two-hybrid system and in a
glutathione S-transferase (GST) pull-down assay. Interestingly, overexpression of the
kinase domain deleted and
kinase-inactive mutants of hMINK beta in human
fibrosarcoma HT1080 cells enhanced cell spreading, actin stress fiber formation, and adhesion to extracellular matrix, as well as decreased cell motility and cell invasion. Furthermore, these mutants also promoted cell-cell adhesion in human
breast carcinoma MCF7 cells, evidenced with cell growth in clusters and increased membrane localization of
beta-catenin, a multifunctional
protein involved in
E-cadherin-mediated cell adhesion. Finally, hMINK beta
protein was found to colocalize with the Golgi apparatus, implicating that hMINK beta might exert its functions, at least in part, through the modulation of intracellular protein transport. Taken together, these results suggest that hMINK beta plays an important role in cytoskeleton reorganization, cell adhesion, and cell motility.