Genomic organization and biosynthesis of secreted and cytoplasmic forms of gelsolin.
Gelsolin is an actin regulatory protein which is unique among vertebrates in that it is found as both an intrinsic cytoplasmic protein and as a secreted plasma protein. We demonstrate that plasma and cytoplasmic gelsolins are derived by alternative transcriptional initiation sites and message processing from a single gene 70 kb long, containing at least 14 exons. Their message and amino acid sequences are identical except at the 5' end/NH2 termini. The cytoplasmic-specific 5' sequence is derived from two exons that encode untranslated sequence, while the plasma message-specific 5' sequence is derived from a single exon that encodes untranslated sequence, the signal peptide, and the first 21 residues of the plasma protein. The two transcriptional initiation sites are separated by greater than or equal to 32 kb. Biosynthetic and RNase protection studies indicate that a number of cell types make both plasma and cytoplasmic gelsolin in widely varying amounts and ratios.
Kwiatkowski
D J
DJ
Department of Medicine, Massachusetts General Hospital, Harvard Medical School, Boston 02114.
Mehl
R
R
Yin
H L
HL
D001483:Base Sequence; D002135:Calcium-Binding Proteins / Q000096:biosynthesis / Q000235:genetics* / Q000378:metabolism; D003001:Cloning, Molecular; D003593:Cytoplasm / Q000378:metabolism; D004247:DNA / Q000235:genetics; D018260:Gelsolin; D005796:Genes; D006801:Humans; D008840:Microfilament Proteins / Q000096:biosynthesis / Q000235:genetics* / Q000378:metabolism; D008969:Molecular Sequence Data; D012333:RNA, Messenger / Q000235:genetics; D012260:Ribonucleases; D014018:Tissue Distribution; D014158:Transcription, Genetic
D002135:Calcium-Binding Proteins; D018260:Gelsolin; D008840:Microfilament Proteins; D012333:RNA, Messenger; D004247:DNA; D012260:Ribonucleases