mRNAs for plasma membrane calcium pump isoforms differing in their regulatory domain are generated by alternative splicing that involves two internal donor sites in a single exon

E. E. Strehler, M. A. Strehler-Page, G. Vogel, E. Carafoli

Research output: Contribution to journalArticle

89 Scopus citations

Abstract

cDNA clones coding for human plasma membrane Ca2+ pump isoforms have been isolated from a fetal skeletal muscle cDNA library. Compared with the sequence of a teratoma cDNA-encoded pump these clones specify isoforms that contain either 29- or 38-amino acid insertions within the calmodulin-binding region. Replacement of two basic arginine residues by an aspartic acid and a glutamine residue could influence the binding of calmodulin to these isoforms. RNase mapping shows that RNA species containing the 29-residue-encoding insertion are particularly abundant in skeletal muscle. The sequences coding for the insertions are present on a single 154-base-pair exon, as demonstrated by an analysis of the corresponding genomic region, and they are included in their respective mRNAs by alternative splicing involving the differential usage of two internal 'cryptic' donor splice sites in the presence of a nearby canonical one. Inclusion of the complete 154-base-pair exon results in an mRNA coding for a pump protein with a shorter C-terminal amino acid sequence that lacks on consensus site for phosphorylation by the cAMP-dependent kinase. Exclusion, inclusion, or partial inclusion of the same exon can thus lead to the production of four different mRNAs from a single gene. When expressed as protein, these mRNAs encode Ca2+ pump isoforms that differ in their C-terminal regulatory domains.

Original languageEnglish (US)
Pages (from-to)6908-6912
Number of pages5
JournalProceedings of the National Academy of Sciences of the United States of America
Volume86
Issue number18
DOIs
StatePublished - Jan 1 1989

ASJC Scopus subject areas

  • General

Fingerprint Dive into the research topics of 'mRNAs for plasma membrane calcium pump isoforms differing in their regulatory domain are generated by alternative splicing that involves two internal donor sites in a single exon'. Together they form a unique fingerprint.

  • Cite this