Growth factor dependent AKT activation and cell migration requires the function of c-K(B)-Ras versus other cellular Ras isoforms. Export

@article{citeulike:813572, abstract = {K-Ras negative fibroblasts are defective in their steady-state expression of MMP-2. This occurs through c-K(B)-Ras dependent regulation of basal levels of AKT activity. In this report, we have extended those studies to demonstrate that in the absence of K-Ras expression, PDGF-BB fails to induce significant AKT activation, though this was not the case in N-Ras negative cells. This phenotype was directly linked to PDGF-dependent cell migration. All of the independently immortalized K-Ras negative cells failed to migrate upon addition of PDGF. Only ectopic expression of c-K(B)-Ras, not c-K(A)-Ras or oncogenic N-Ras could restore both PDGF-dependent AKT activation and cell migration. Since most Ras binding partners can interact with all Ras isoforms, the specificity of PDGF-dependent activation of AKT and enhanced cell migration suggests these outcomes are likely to be regulated through a c-K(B)-Ras specific binding partner. Others have published that of the four Ras isoforms, only K(B)-Ras can form a stable complex with calmodulin (CaM). Along those lines, we provide evidence that (1) PDGF addition results in increased levels of a complex between c-K(B)-Ras and CaM and (2) the biological outcomes that are strictly dependent on c-K(B)-Ras (AKT activation and cell migration) are blocked by CaM antagonists. The PDGF dependent activation of ERK is unaffected by the absence of K(B)-Ras and presence of CaM antagonists. This is the first example of a linkage between a specific biological outcome, cell migration, and the activity of a single Ras isoform, c-K(B)-Ras.}, address = {Dept. Cell Biology, NC10, Cleveland Clinic Foundation, Cleveland, OH 44195.}, author = {Liao, Jinhui and Planchon, Sarah M M. and Wolfman, Janice C C. and Wolfman, Alan}, citeulike-article-id = {813572}, citeulike-linkout-0 = {http://dx.doi.org/10.1074/jbc.M600668200}, citeulike-linkout-1 = {http://view.ncbi.nlm.nih.gov/pubmed/16908523}, citeulike-linkout-2 = {http://www.hubmed.org/display.cgi?uids=16908523}, day = {14}, doi = {10.1074/jbc.M600668200}, issn = {0021-9258}, journal = {J Biol Chem}, keywords = {activation, akt, downstream, erk, k-ras, signaling}, month = {August}, posted-at = {2006-08-23 11:41:39}, priority = {2}, title = {Growth factor dependent AKT activation and cell migration requires the function of c-K(B)-Ras versus other cellular Ras isoforms.}, url = {http://dx.doi.org/10.1074/jbc.M600668200}, year = {2006} }

TY - JOUR ID - citeulike:813572 L3 - citeulike-article-id:813572 N2 - K-Ras negative fibroblasts are defective in their steady-state expression of MMP-2. This occurs through c-K(B)-Ras dependent regulation of basal levels of AKT activity. In this report, we have extended those studies to demonstrate that in the absence of K-Ras expression, PDGF-BB fails to induce significant AKT activation, though this was not the case in N-Ras negative cells. This phenotype was directly linked to PDGF-dependent cell migration. All of the independently immortalized K-Ras negative cells failed to migrate upon addition of PDGF. Only ectopic expression of c-K(B)-Ras, not c-K(A)-Ras or oncogenic N-Ras could restore both PDGF-dependent AKT activation and cell migration. Since most Ras binding partners can interact with all Ras isoforms, the specificity of PDGF-dependent activation of AKT and enhanced cell migration suggests these outcomes are likely to be regulated through a c-K(B)-Ras specific binding partner. Others have published that of the four Ras isoforms, only K(B)-Ras can form a stable complex with calmodulin (CaM). Along those lines, we provide evidence that (1) PDGF addition results in increased levels of a complex between c-K(B)-Ras and CaM and (2) the biological outcomes that are strictly dependent on c-K(B)-Ras (AKT activation and cell migration) are blocked by CaM antagonists. The PDGF dependent activation of ERK is unaffected by the absence of K(B)-Ras and presence of CaM antagonists. This is the first example of a linkage between a specific biological outcome, cell migration, and the activity of a single Ras isoform, c-K(B)-Ras. JF - J Biol Chem SN - 0021-9258 AD - Dept. Cell Biology, NC10, Cleveland Clinic Foundation, Cleveland, OH 44195. TI - Growth factor dependent AKT activation and cell migration requires the function of c-K(B)-Ras versus other cellular Ras isoforms. KW - activation KW - akt KW - downstream KW - erk KW - k-ras KW - signaling AU - Liao, Jinhui AU - Planchon, Sarah M AU - Wolfman, Janice C AU - Wolfman, Alan PY - 2006/08/14/ UR - http://dx.doi.org/10.1074/jbc.M600668200 ER -