The @entity5605 regulated non-receptor @entity669 kinase ACK-2 has been associated with integrin signaling. In this report, the effect of ACK-2 on the modulation of cell spreading and motility was examined. HeLa cells expressing epitope-tagged wild type ACK-2 showed a slower rate of spreading on fibronectin when compared with untransfected cells. An ACK-2 protein lacking its SH3 domain was still capable of modulating HeLa cell spreading suggesting that its @entity669 kinase activity is sufficient to induce the observed phenotype. The ACK-2 effect on the rate of cell spreading did not involve inhibition of integrin-mediated activation of PI-3K signaling, since it did not alter membrane translocation of a GFP-PH-AKT domain (AKT pleckstrin homology domain) used as a reporter for PI-3K products induced by cell adhesion. The ACK-2 effect appears to be upstream from the adapter protein @entity4987 , since co-expression of @entity4987 and ACK-2 results in a neutralization of ACK-2 mediated effects on HeLa cell spreading. Similarly, co-expression of @entity20336 , which interacts with the adapter protein @entity4987 , with ACK-2, also results in a partial reversion of the ACK-2 effects on cell spreading. @entity4987 mediated reversal of the ACK-2 induced phenotype requires the activity of the small GTPase, @entity9704 . Co-expression of ACK-2 and @entity4987 with a dominant negative form of @entity9704 reverses the neutralization by @entity4987 suggesting that @entity4987 mediated activation of @entity9704 is required. However, an active form of @entity9704 is not sufficient to reverse the ACK-2 phenotype by itself. A role for @entity5180 in ACK-2 effects was also established. An activated @entity5180 protein neutralized the ACK-2 mediated inhibition of cell spreading. A direct measurement of cell motility by either a modified Boyden chamber or wounding assay demonstrates that ACK-2 overexpression increases the motility of the cells. These results suggest that ACK-2 modulates HeLa cells spreading upstream of pathways regulated by @entity4987 and that ACK-2 may regulate cell motility by controlling the activation of small GTPases such as @entity9704 and @entity5180 .

Modulation of HeLa cells spreading by the non-receptor XXXX kinase ACK-2.

@entity9704 :: ('5906', 'Gene') :: ['Rap1'] @entity4987 :: ('1398', 'Gene') :: ['CrkII'] @entity5605 :: ('998', 'Gene') :: ['CDC42'] @entity5180 :: ('5879', 'Gene') :: ['Rac1'] @entity669 :: ('CHEBI:18186', 'Chemical') :: ['tyrosine'] @entity20336 :: ('9564', 'Gene') :: ['p130Cas']
@entity669 :: (CHEBI:18186,Chemical) :: ['tyrosine']
