Organization of the human PTK7 gene encoding a receptor protein tyrosine kinase-like molecule and alternative splicing of its mRNA.
Protein tyrosine kinase-7 (PTK7) is a receptor protein tyrosine kinase (RPTK)-like molecule that contains a catalytically inactive tyrosine kinase domain. We report here the genomic structure of the human PTK7 gene by screening a BAC library and DNA sequencing. The PTK7 gene is organized into 20 exons. All of the splicing junctions followed the conserved GT/AG rule. The exon-intron structure of the PTK7 gene in the region that encodes the catalytic domain was distinct from those of other RPTKs with strong homology. The 5'-flanking sequence of the PTK7 gene contains two GC boxes that concatenate Sp1 binding motifs, but does not contain either the TATA or CAAT consensus sequence. Using a luciferase reporter assay, it was demonstrated that the 883-bp 5'-flanking sequence is functional as a promoter of the PTK7 gene. We identified four new splicing variants in testis that could be derived from alternative splicing of exons 8-10, 10, a part of 12-13, and 16. The expression patterns of the splicing variants in the hepatoma and colon cancer cells were different from those of the testis. Our findings suggest that PTK7 is evolutionarily distinct from other RPTKs, and that the alternative splicing of PTK7 mRNA may contribute to its diverse function in cell signaling.
Jung
Jae Won
JW
National Research Laboratory of Cellular Biochemistry, Department of Biochemistry, College of Science, and Protein Network Research Center, Yonsei University, Seoul, South Korea.
Ji
Ae Ri
AR
Lee
Jonghyeob
J
Kim
Ung Jin
UJ
Lee
Seung Taek
ST
D024506:5' Flanking Region; D017398:Alternative Splicing; D000595:Amino Acid Sequence; D001483:Base Sequence; D015815:Cell Adhesion Molecules / Q000032:analysis / Q000096:biosynthesis / Q000235:genetics*; D003001:Cloning, Molecular; D005091:Exons; D015870:Gene Expression; D006801:Humans; D008297:Male; D008969:Molecular Sequence Data; D011401:Promoter Regions, Genetic / Q000502:physiology; D020033:Protein Isoforms / Q000032:analysis / Q000235:genetics; D012333:RNA, Messenger / Q000032:analysis / Q000096:biosynthesis / Q000378:metabolism*; D020794:Receptor Protein-Tyrosine Kinases / Q000032:analysis / Q000096:biosynthesis / Q000235:genetics*; D015183:Restriction Mapping; D016415:Sequence Alignment; D013737:Testis / Q000378:metabolism; D014407:Tumor Cells, Cultured
D015815:Cell Adhesion Molecules; D020033:Protein Isoforms; D012333:RNA, Messenger; C096905:PTK7 protein, human; D020794:Receptor Protein-Tyrosine Kinases