Epidermal growth factor (EGF) induces cell proliferation in a variety of cell types by binding to a prototype transmembrane tyrosine kinase receptor. Ligation of this receptor by EGF activates Erk1 an Show more
Epidermal growth factor (EGF) induces cell proliferation in a variety of cell types by binding to a prototype transmembrane tyrosine kinase receptor. Ligation of this receptor by EGF activates Erk1 and Erk2, members of the mitogen-activated protein (MAP) kinase family, through a Ras-dependent signal transduction pathway. Despite our detailed understanding of these events, the exact mechanism by which EGF causes cells to proliferate is unclear. Big MAP kinase (Bmk1), also known as Erk5, is a member of the MAP kinase family that is activated in cells in response to oxidative stress, hyperosmolarity and treatment with serum. Here we show that EGF is a potent activator of Bmk1. In contrast to Erk1/2, EGF-mediated activation of Bmk1 occurs independently of Ras and requires the MAP-kinase kinase Mek5. Expression of a dominant-negative form of Bmk1 blocks EGF-induced cell proliferation and prevents cells from entering the S phase of the cell cycle. These results demonstrate that Bmk1 is part of a distinct MAP-kinase signalling pathway that is required for EGF-induced cell proliferation and progression through the cell cycle. Show less
Big MAP kinase 1 (BMK1), also known as ERK5, is a mitogen-activated protein (MAP) kinase member whose biological role is largely undefined. We have shown previously that the activity of BMK1 in rat sm Show more
Big MAP kinase 1 (BMK1), also known as ERK5, is a mitogen-activated protein (MAP) kinase member whose biological role is largely undefined. We have shown previously that the activity of BMK1 in rat smooth muscle cells is up-regulated by oxidants. Here, we describe a constitutively active form of the MAP kinase kinase, MEK5(D), which selectively activates BMK1 but not other MAP kinases in vivo. Through utilization of MEK5(D), we have determined that a member of the MEF2 transcription factor family, MEF2C, is a protein substrate of BMK1. BMK1 dramatically enhances the transactivation activity of MEF2C by phosphorylating a serine residue at amino acid position 387 in this transcription factor. Serum is also a potent stimulator of BMK1-induced MEF2C phosphorylation, since a dominant-negative form of BMK1 specifically inhibits serum-induced activation of MEF2C. One consequence of MEF2C activation is increased transcription of the c-jun gene. Taken together, these results strongly suggest that in some cell types the MEK5/BMK1 MAP kinase signaling pathway regulates serum-induced early gene expression through the transcription factor MEF2C. Show less
Female gamete abortion in Indica-Japonica crosses of rice was earlier identified to be due to an allelic interaction at the S-5 locus on chromosome 6. Recently, in other crosses of rice, similar allel Show more
Female gamete abortion in Indica-Japonica crosses of rice was earlier identified to be due to an allelic interaction at the S-5 locus on chromosome 6. Recently, in other crosses of rice, similar allelic interactions were found at loci designated as S-7 and S-8, located on chromosomes 7 and 6 respectively. All of them are independent of each other. At the S-5 locus, Indica and Japonica rice have S-5 (i) and S-5 (j) alleles respectively and Javanicas, such as Ketan Nangka, have a neutral allele S-5 (n) .The S-5 (i) /S-5 (j) genotype is semi-sterile due to partial abortion of female gametes carrying S-5 (j) , but both the S-5 (n) /S-5 (i) and S-5 (n) /S-5 (j) genotypes are fertile. The S-5 (n) allele is thus a "wide-compatibility gene" (WCG), and parents homozygous for this allele are called wide-compatible varieties (WCV). Such parents when crossed with Indica or Japonica varieties do not show F1 hybrid sterility. Wide-compatible parents have been used to overcome sterility barriers in crosses between Indica and Japonica rice. However, a Javanica variety, Ketan Nangka (WCV), showed typical hybrid sterility when crossed to the Indian varieties N22 and Jaya. Further, Dular, another WCV from India, showed typical hybrid sterility when crossed to an IRRI line, IR2061-628-1-6-4-3(IR2061-628). By genetic analyses using isozyme markers, a new locus causing hybrid sterility in crosses between Ketan Nangka and the Indicas was located near isozyme loci Est-1 and Mal-1 on chromosome 4, and was designated as S-9. Another new locus for hybrid sterility in the crosses between Dular and the IR2061-628 was identified and was found linked to four isozyme loci, Sdh-1, Pox-2, Acp-1 and Acp-2, on chromosome 12. It was designated as S-15. On the basis of allelic interactions causing female-gamete abortion, two alleles were found at S-9, S-9 (kn) in Ketan Nangka and S-9 (i) in N22 and Jaya. In the heterozygote, S-9 (kn) /S-9 (i) , which was semisterile, female gametes carrying S-9 (kn) were aborted. The hybrid of Dular and IR2061-628, with a genetic constitution of S-15 (Du) /S-15 (i) , was semi-sterile and the female gametes carrying S-15 (Du) were aborted. A Japonica tester variety, Akihikari, and an Indica variety, IR36, were found to have neutral alleles, S-9 nand S-15 n, at these loci, in addition to S-7 nand at S-7. The accumulation of three neutral alleles into a breeding line should help solve the hybrid sterility problem in wide crosses of rice. Show less