PT - JOURNAL ARTICLE AU - Takayuki Kohno AU - Takafumi Ninomiya AU - Shin Kikuchi AU - Takumi Konno AU - Takashi Kojima TI - Staurosporine Induces Formation of Two Types of Extra-Long Cell Protrusions: Actin-Based Filaments and Microtubule-Based Shafts AID - 10.1124/mol.114.096982 DP - 2015 Jan 01 TA - Molecular Pharmacology PG - mol.114.096982 4099 - http://molpharm.aspetjournals.org/content/early/2015/02/13/mol.114.096982.short 4100 - http://molpharm.aspetjournals.org/content/early/2015/02/13/mol.114.096982.full AB - Staurosporine (STS) has been known as a classical PKC inhibitor and is a broad-spectrum inhibitor targeting over 250 protein kinases. In this study, we observed that STS treatment induced drastic morphological changes such as elongation of a very large number of non-branched, actin-based long cell protrusions that reached up to 30 μm in an hour without caspase activation or PARP cleavage in fibroblasts and epithelial cells. These cell protrusions were elongated not only from the free cell edge but also from the cell-cell junctions. The elongation of STS-dependent protrusions was required for ATP hydrolysis and was dependent on Myo10 and fascin, but independent of Cdc42 and VASP. Interestingly, in the presence of an actin polymerization inhibitor, namely cytochalasin D, latrunculin A, or jasplakinolide, STS treatment induced excess tubulin polymerization, which resulted in the formation of many extra-long microtubule (MT)-based protrusions towards the outside of the cell. The unique MT-based protrusions were thick and linear compared to the STS-induced filaments or stationary filopodia. These protrusions composed of microtubules have been scarcely observed in cultured non-neuronal cells. Taken together, our findings revealed that STS-sensitive kinases are essential for maintenance of normal cell morphology, and a common unidentified molecular mechanism is involved in the formation of following two different types of protrusions: actin-based filaments and MT-based shafts.