科研之友
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摘要
TGF beta (transforming growth factor beta) super-family signalling is critical both for early embryonic development and later for tissue homoeostasis in adult organisms. The use of gene-disruption techniques in mice has been essential to understanding the functional roles of the components of the pathways downstream of TGF beta superfamily ligands, in particular, the receptors and the Smads that transduce signals from the plasma membrane to file nucleus. Smad2 functions downstream of TGF beta, Activin and Nodal, and a number of Sina(12 Mutant mice have been generated by different laboratories. Although in all cases these Smad2-deficient mice were embryonic lethal, those created by deletion of the first coding exon survived longer than those generated by replacing part of the MH (Mad homology) 1 domain or deleting all or part of the MH2 domain. Moreover,, they displayed a less severe phenotype, as they were capable of transiently inducing mesoderm. In the present study, we show that embryonic fibroblasts taken from the Smad2 mutant mice created by deletion of the first coding exon express a small amount of in N-terminally truncated Smad2 protein. We show this protein results from internal initiation at Met(241) and encodes the entire MH2 domain and the C-terminal part of the linker. We demonstrate that this protein is incorporated into Smad heteromeric complexes, call interact with DNA-binding transcription factors and thereby call mediate TGF beta-induced transcriptional activation from a number of TGF beta-responsive elements. We propose that. this functional truncated Smad2 protein can partially compensate for the loss of full-length Smad2, thereby providing all explanation for the differing phenotypes of Smad2 mutant mice.
- 出版日期2009-1-1
