D. M. Helfman

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Mutations in the Schizosaccharomyces pombe cdc8 gene impair cytokinesis. Here we clone cdc8+ and find that it encodes a novel tropomyosin. Gene disruption results in lethal arrest of the cell cycle, but spore germination, cell growth, DNA replication and mitosis are all unaffected. Haploid cdc8 gene disruptants are rescued by expression of a fibroblast(More)
The opposing effects of SF2/ASF and heterogeneous nuclear ribonucleoprotein (hnRNP) A1 influence alternative splicing in vitro. SF2/ASF or hnRNP A1 complementary DNAs were transiently overexpressed in HeLa cells, and the effect on alternative splicing of several cotransfected reporter genes was measured. Increased expression of SF2/ASF activated proximal 5'(More)
Caldesmon is known to inhibit the ATPase activity of actomyosin in a Ca(2+)-calmodulin-regulated manner. Although a nonmuscle isoform of caldesmon is widely expressed, its functional role has not yet been elucidated. We studied the effects of nonmuscle caldesmon on cellular contractility, actin cytoskeletal organization, and the formation of focal adhesions(More)
Research during the past couple of years has provided important new information as to how the actin cytoskeleton contributes to growth control in both normal and transformed cells. The cytoskeleton can no longer be viewed as simply a structural framework playing a role in cell shape and motile events such as cell movement, intracellular transport,(More)
Tropomyosins are a family of actin filament binding proteins. They have been identified in many organisms, including yeast, nematodes, Drosophila, birds and mammals. In metazoans, different forms of tropomyosin are characteristic of specific cell types. Most non-muscle cells, such as fibroblasts, express five to eight isoforms of tropomyosins. The various(More)
p90 ribosomal S6 kinase (RSK1) is an effector of both Ras/MEK/MAPK and PI3K/PDK1 pathways. We present evidence that RSK1 drives p27 phosphorylation at T198 to increase RhoA-p27 binding and cell motility. RSK1 activation and p27pT198 both increase in early G(1). As for many kinase-substrate pairs, cellular RSK1 coprecipitates with p27. siRNA to RSK1 and RSK1(More)
In the rat beta-tropomyosin (beta-TM) gene, exons 6 and 7 are spliced alternatively in a mutually exclusive manner. Exon 6 is included in mRNA encoding nonmuscle TM-1, whereas exon 7 is used in mRNA encoding skeletal muscle beta-TM. Previously, we demonstrated that a six nucleotide mutation at the 5' end of exon 7, designated as ex-1, activated exon 7(More)
Previous studies of alternative splicing of the rat beta-tropomyosin gene have shown that nonmuscle cells contain factors that block the use of the skeletal muscle exon 7 (Guo, W., Mulligan, G. J., Wormsley, S., and Helfman, D. M. (1991) Genes & Dev. 5, 2095-2106). Using an RNA mobility-shift assay we have identified factors in HeLa cell nuclear extracts(More)
Cell-substratum interactions trigger key signaling pathways that modulate growth control and tissue-specific gene expression. We have previously shown that abolishing adhesive interactions by suspension culture results in G(0) arrest of myoblasts. We report that blocking intracellular transmission of adhesion-dependent signals in adherent cells mimics the(More)