A rare mRNA variant of the human lymphocyte-specific protein tyrosine kinase LCK gene with intron B retention and exon 7 skipping encodes a putative protein with altered SH3-dependent molecular interactions.
A rare mRNA variant of the human lymphocyte-specific protein tyrosine kinase LCK gene that retains intron B and excludes exon 7 (B+7-) due to alternative splicing of the canonical LCK transcripts was identified and characterized. LCK B+7- mRNA is detected in all tested peripheral blood T lymphocytes total RNA samples but is apparently sequestered in the nucleus. The presence of intron B sequence does not disrupt the reading frame and results in the insertion of 58 aminoacids, containing a proline-rich region just upstream of p56lck SH3 domain. This putative isoform encodes an unstable 516 aminoacids protein (LckB+7-) which can be expressed in transfected COS-7 cells. Furthermore in Jurkat T cell extracts, a recombinant intron B plus SH3 p56lck domain fails to interact with some TCR-induced tyrosine phosphorylated polypeptides and known p56lck partners such as Sam68 and c-Cbl. The biological function of this rare messenger remains to be elucidated.
Nervi
Solange
S
Institut de Cancérologie de Marseille, UMR599 INSERM-Institut Paoli-Calmettes-Université de la Méditerranée, 27 boulevard Leï Roure, 13009 Marseille, France.
Guinamard
Rodolphe
R
Delaval
Bénédicte
B
Lécine
Patrick
P
Vialettes
Bernard
B
Naquet
Philippe
P
Imbert
Jean
J
D017398:Alternative Splicing; D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D015153:Blotting, Western; D019556:COS Cells; D002478:Cells, Cultured; D002522:Chlorocebus aethiops; D003001:Cloning, Molecular; D018076:DNA, Complementary / Q000737:chemistry / Q000235:genetics; D006801:Humans; D007438:Introns / Q000235:genetics; D007527:Isoenzymes / Q000235:genetics / Q000378:metabolism; D019169:Jurkat Cells; D019860:Lymphocyte Specific Protein Tyrosine Kinase p56(lck) / Q000235:genetics* / Q000378:metabolism; D008969:Molecular Sequence Data; D016254:Mutagenesis, Insertional; D011485:Protein Binding; D012333:RNA, Messenger / Q000235:genetics* / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D016415:Sequence Alignment; D017422:Sequence Analysis, DNA; D012689:Sequence Homology, Nucleic Acid; D013601:T-Lymphocytes / Q000166:cytology / Q000201:enzymology / Q000378:metabolism; D014158:Transcription, Genetic / Q000235:genetics; D018909:src Homology Domains / Q000235:genetics*
D018076:DNA, Complementary; D007527:Isoenzymes; D012333:RNA, Messenger; D019860:Lymphocyte Specific Protein Tyrosine Kinase p56(lck)