This is not quite as settled as Peter's post makes it look. See my reply here:
Message 27137940
One study that seems to go the other way, aside from the one quoted in my reply . . .
>>Biochem Biophys Res Commun. 1995 Aug 4;213(1):273-81.
Molecular characterization of the murine syk protein tyrosine kinase cDNA, transcripts and protein.
Flück M, Zürcher G, Andres AC, Ziemiecki A.
Department of Clinical Research, University of Bern, Switzerland.
Abstract
Using a RT-PCR based cloning strategy and conventional cDNA library screening we have cloned the murine syk cDNA. Sequence analysis of the 5350bp full length cDNA revealed a 5' untranslated region (UTR) of 477bp, an open reading frame of 1884bp and an unusually long 3' UTR of 2989bp containing a polyadenylation signal. The cDNA encodes a putative protein of 628 amino acids with two SH2 domains located N-terminally of the protein tyrosine kinase domain. The highest overall homology, 98%, was observed to the rat syk. Northern blot analysis revealed that the murine syk protein is encoded by two transcripts of approximately 5.4 and 3.5kb, the difference in size being attributable to differences in the 3' UTR. Rabbit antisera raised against a pGEX-syk bacterial fusion protein recognized specifically a protein of approximately 67kd with intrinsic protein tyrosine kinase activity in lymphoid cell extracts. The size of the syk protein could be confirmed by in vitro transcription/translation of the full length clone. Expression of syk was found in a variety of mouse organs with the highest levels in spleen, heart, mammary gland and thymus and in several lymphoid cell lines. The majority of the expression observed in whole mammary glands originated from the lymph node. Upregulated expression of syk was observed in aggressive, metastasizing mammary gland tumours but not in well differentiated, non-metastasizing tumors.<<
See also
"Spleen Tyrosine Kinase (Syk), a Novel Target of Curcumin, Is Required for B Lymphoma Growth"
jimmunol.org
Which probably explains why lymphoma is still being studied in human trails of FosD.
I'll admit the preponderance of evidence leans towards SYK inhibition promoting breast cancer.
It might be worth pinging Rigel IR to see what their stance is on this, since no analyst has taken Peter's ball and run with it. At least, unlike lorcaserin, the studies are out in the open!
Cheers, Tuck |
