The extent of enrichment by translocation along the microtubule would depend on formation of multimotor complexes or attachment of the motors to other proteins that might enhance processivity. Our data show that Klp5/6 does not cause catastrophe of dynamic microtubules in vitro whereas Klp5/6 in its natural in vivo environment does accelerate microtubule catastrophe. Clearly the cellular context is required for the catastrophase activity of Klp5/ 6. It is possible that our Klp5/6 constructs lack an activating posttranslational modification or binding partner found in cells. However, we doubt this is the case since our constructs are active, in that they have microtubule and tubulin stimulated ATPase activity and can translocate microtubules. Instead, we suggest that the missing factor in our in vitro assays is mechanical compression of the microtubule tip. In S. pombe, microtubule catastrophes occur almost exclusively in the end zone of the cell, with the microtubule tip in contact with the cell wall and in compression. Mechanical force can trigger microtubule catastrophe in vitro and a role for force has been suggested in S. pombe. The growing plus end of a dynamic microtubule is thought to carry a small sheet of protofilaments that has yet to close into a tube, that may resemble the nucleus formed at the outset of microtubule assembly. We speculate that Klp5 and Klp6 would stabilise the sheet in the absence of external forces by linking heterodimers, thus promoting nucleation. However at cell ends Klp5 and 6 would no longer stabilise but rather destabilise the microtubule. This might occur through the same property of gripping the tipsheet if Klp5/6 were, for example, to link to the cell end and apply enhanced force to the already compressed microtubule. We propose that the effect of this additional destabilising force exerted by Klp5/6 on the microtubule is sufficient to overcome the stabilising effect of Klp5/6 binding, further increasing the catastrophe frequency. The erythropoietin-producing hepatocellular receptors and their ligands, ephrins comprise the largest subfamily of receptor tyrosine kinases, playing an important role in physiology such as embryogenesis, organ development, and angiogenesis as well as implicated in several types of cancers. Among different classes of ephrins, ephrin-B2 is primarily expressed in arterial endothelial cells and neovasculature, forming a bidirectional signal with its cognate receptor EphB4, which is mainly expressed in venous endothelial cell. The importance of such interaction in a developmental process has been demonstrated by impaired angiogenesis and ultimately embryonic lethality in mice due to homozygous mutation of ephrin-B2 or EphB4. The role of EphB4 and ephrin-B2 also extends to tumor growth and angiogenesis. Inhibition of their interaction by EphB4 antibody or extracellular fragment of EphB4 can inhibit tumor angiogenesis and tumor growth. Ephrin-B2 is involved in vascular endothelial growth factor signaling, through the internalization of VEGF receptor in all endothelial cell types during physiological and pathological angiogenesis, and could be upregulated in VEGF-treated endothelial cells. Expression of ephrin-B2 along with EphB4 was found to be higher in many tumors including colorectal, breast, ovarian, and lung, serving as a poor Compound Library prognostic marker.