Here's the abstract from the story Stuart posted. An NPR report this morning described the scientist as saying the government offered as "much money as he needed" to follow up. FWIW, of the biotechs, VRTX has the broadest experience with kinases.
Copyright © 2001 Elsevier Science Ltd. All rights reserved.
Current Biology, Vol 11, 1503-1511, October 2001
Research paper
Kif1C, a kinesin-like motor protein, mediates mouse macrophage resistance to anthrax lethal factor
James W. Watters*, Ken Dewar‡, Jessica Lehoczky‡, Victor Boyartchuk*, and William F. Dietrich*,†
* Department of Genetics, Harvard Medical School, Boston, MA 02115 USA
† Howard Hughes Medical Institute, Harvard Medical School, Boston, MA 02115 USA
‡ Whitehead Institute for Biomedical Research, Cambridge, MA 02142 USA
Correspondence:
William F. Dietrich Phone: (617) 432-6785
Fax: (617) 432-3993
dietrich@rascal.med.harvard.edu
Background: Inbred mouse strains exhibit striking differences in the susceptibility of their macrophages to the effects of anthrax lethal toxin (LeTx). Previous data has shown that this difference in susceptibility lies downstream of toxin entry into macrophages. A locus controlling this phenotype, called Ltxs1, has been mapped to chromosome 11, but the responsible gene has not been identified.
Results: Here, we report the identification of the Ltxs1 gene as Kif1C, which encodes a kinesin-like motor protein of the UNC104 subfamily. Kif1C is the only gene in the Ltxs1 interval exhibiting polymorphisms between susceptible and resistant strains. Multiple alleles of Kif1C determine the susceptibility or resistance of cultured mouse macrophages to LeTx. Treatment of resistant macrophages with brefeldin-A (which alters the cellular localization of Kif1C) induces susceptibility to LeTx, while ectopic expression of a resistance allele of Kif1C in susceptible macrophages causes a 4-fold increase in the number of cells surviving LeTx treatment. We also show that cleavage of map kinase kinase 3, a target of LeTx proteolysis, occurs in resistant cells.
Conclusions: We conclude that mutations in Kif1C are responsible for the differences in the susceptibility of inbred mouse macrophages to LeTx and that proper Kif1C function is required for LeTx resistance. Since the LeTx-mediated proteolysis of map kinase kinase 3 occurs even in resistant cells, Kif1C does not affect cellular entry or processing of LeTx and likely influences events occurring later in the intoxication pathway.<i/> |
