Abstract

Protein tyrosine kinases (PTKs) are implicated in the control of cell growth by virtue of their frequent appearance as products of retroviral oncogenes, as intracellular signal transducers, and as growth factor receptors or components thereof. The knowledge of the structure and sequence of family genes encoding PTKs is still limited. To date, the complete genomic structure of human src family members is only available for the C-FGR gene (encoding p55 Fgr, PTK). Sequence analysis and characterization of the intron/exon organization of the human HCK gene, encoding a hemopoietic-specific cell PTK of the src-related family, revealed a length of over 16 kb for the seven 3′-exons. All intron/exon splice junctions agree with the GT/AG rule. In each case where a boundary occurs at a Gly codon, GGG or GGA, the triplet is split between the first and second nucleotide (nt). A total of eight complete and one partial Alu repeats were identified within the introns. The nt sequence of the genomic clones resolves existing discrepancies among two published sequences of HCK cDNAs. Human HCK, S-SRC (encoding p60 Src PTK), C-FGR and LCK (encoding p56 Lck, PTK) genes thus share very similar exon/intron structures for the conserved exons. These results provide additional evidence that the different PTKs of the src-like family most likely arose by duplication of an ancestral src-like gene.

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