Identification and characterization of a functional murine FLT3 isoform produced by exon skipping.
The FLT3 gene encodes an hematopoietic receptor related to the receptors for colony-stimulating factor 1, FMS, and for Steel factor, KIT. The extracellular part of these molecules is exclusively composed of five immunoglobulin (Ig)-like domains, designated 1 to 5, from the amino terminus to the carboxyl terminus of the extracellular region. We have isolated a unique murine FLT3 cDNA that codes for a variant isoform of FLT3, devoid of the fifth Ig-like domain, by comparison with the prototypic form. The corresponding mRNA is the result of a splicing event that leads to the elimination of two coding exons. mRNA coding for this variant was detected in almost all the tissues expressing the mRNA coding for the prototypic molecule, although at a lower level. Ligand-induced tyrosine phosphorylation of the two isoforms was equivalent in COS-1 transfected cells, indicating that the fifth Ig-like domain is not strictly necessary for either ligand-binding or kinase activation.
Lavagna
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C
Laboratoire d'Oncologie Moléculaire, INSERM U.119, Marseille, France.
Marchetto
S
S
Birnbaum
D
D
Rosnet
O
O
D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D002460:Cell Line; D002522:Chlorocebus aethiops; D017931:DNA Primers; D005091:Exons; D015870:Gene Expression; D006801:Humans; D007668:Kidney; D051379:Mice / Q000235:genetics*; D008969:Molecular Sequence Data; D008970:Molecular Weight; D019000:Phosphotyrosine; D016133:Polymerase Chain Reaction; D011487:Protein Conformation; D011518:Proto-Oncogene Proteins / Q000096:biosynthesis* / Q000737:chemistry / Q000235:genetics*; D012333:RNA, Messenger / Q000032:analysis / Q000096:biosynthesis; D020794:Receptor Protein-Tyrosine Kinases / Q000096:biosynthesis* / Q000737:chemistry / Q000235:genetics*; D011956:Receptors, Cell Surface / Q000096:biosynthesis / Q000235:genetics; D011994:Recombinant Proteins / Q000096:biosynthesis / Q000737:chemistry / Q000378:metabolism; D017386:Sequence Homology, Amino Acid; D014162:Transfection; D014443:Tyrosine / Q000031:analogs & derivatives / Q000032:analysis / Q000378:metabolism; D051941:fms-Like Tyrosine Kinase 3
D017931:DNA Primers; D011518:Proto-Oncogene Proteins; D012333:RNA, Messenger; D011956:Receptors, Cell Surface; D011994:Recombinant Proteins; D019000:Phosphotyrosine; D014443:Tyrosine; C497970:FLT3 protein, human; C497971:Flt3 protein, mouse; D020794:Receptor Protein-Tyrosine Kinases; D051941:fms-Like Tyrosine Kinase 3