Silicon Investor (SI) -- The First Internet Community

STOCKTALK

We've detected that you're using an ad content blocking browser plug-in or feature. Ads provide a critical source of revenue to the continued operation of Silicon Investor. We ask that you disable ad blocking while on Silicon Investor in the best interests of our community. If you are not using an ad blocker but are still receiving this message, make sure your browser's tracking protection is set to the 'standard' level.

Biotech / Medical : Kosan BioSciences -- KOSN -- Ignore unavailable to you. Want to Upgrade?

To: tuck who wrote (727)	9/21/2006 4:49:05 PM
From: mopgcw	Respond to of 933

it has been on a nice run here, so was able to establish the lower basis without taking the loss, which is nice. wonder who the buyer is...

To: tuck who wrote (727)	11/4/2006 2:10:18 PM
From: tuck	Respond to of 933

[PDGFR alpha is destabilized by geldanamycins in cancer cells] >> J Biol Chem. 2006 Nov 1; [Epub ahead of print] The platelet derived growth factor receptor alpha is destabilized by geldanamycins in cancer cells. Matei D, Satpathy M, Cao L, Lai YC, Nakshatri H, Donner DB. Indiana University, Indianapolis, IN 46202. The heat shock protein HSP90 serves as a chaperone for receptor protein kinases, steroid receptors and other intracellular signaling molecules. Targeting HSP90 with ansamycin antibiotics disrupts the normal processing of clients of the HSP90 complex. The PDGFRa is a tyrosine kinase receptor upregulated and activated in several malignancies. Here we show that the PDGFRa forms a complex with HSP90 and the co-chaperone cdc37 in ovarian, glioblastoma and lung cancer cells. Treatment of cancer cell lines expressing the PDGFRa with the HSP90 inhibitor 17-allylamino-17-demethoxygeldanamycin (17-AAG) promotes degradation of the receptor. Likewise, phospho-Akt, a downstream target, is degraded after treatment with 17-AAG. In contrast, PDGFRa expression is not affected by 17-AAG in normal human smooth muscle cells (HSMC) or 3T3 fibroblasts. PDGFRa degradation by 17-AAG is inhibited by the proteasome inhibitor MG132. High molecular weight, ubiquitinated forms of the receptor are detected in cells treated with 17-AAG and MG132. Degradation of the receptor is also inhibited by a specific neutralizing antibody to the PDGFRa, but not by a neutralizing antibody to PDGF or by Gleevec. Ultimately, PDGFRa mediated cell proliferation is inhibited by 17-AAG. These results show that 17-AAG promotes PDGFRa degradation selectively in transformed cells. Thus, not only mutated tyrosine kinases, but also overexpressed receptors in cancer cells can be targeted by 17-AAG.<< Cheers, Tuck