Genomic organization of human myotonic dystrophy kinase-related Cdc42-binding kinase alpha reveals multiple alternative splicing and functional diversity.
Myotonic dystrophy kinase-related Cdc42-binding kinase alpha (MRCKalpha) is a Cdc42/Rac interactive binding-containing serine/threonine kinase with multiple functional domains. Its roles in the regulation of peripheral actin reorganization in HeLa cells and NGF-induced neurite outgrowth in PC12 cells have been documented. Here we report the characterization of the genomic structure and alternative splicing of the human counterpart. Human MRCKalpha gene is located on chromosome 1q42.1, spanning a genomic region of 250-300 kb and is composed of 41 exons. Four exons in the internal variable region and six in the 3' end were found to undergo extensive alternative splicing, giving rise to 96 possible transcripts of different combinations. The region of the internal splice site that defines a variable region in between two functional domains of opposite regulatory effects on MRCKalpha catalytic activity, and the 3' end splice site that generates variants with differential GTPase binding activity suggest a role for these alternative splicing events in MRCKalpha regulation.
Tan
Ivan
I
Glaxo-IMCB Group, Institute of Molecular and Cell Biology, 30 Medical Drive, Singapore 117609, Singapore.
Cheong
Albert
A
Lim
Louis
L
Leung
Thomas
T
D020413:3' Untranslated Regions / Q000235:genetics; D017398:Alternative Splicing; D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D004247:DNA / Q000737:chemistry / Q000235:genetics; D005091:Exons; D005796:Genes / Q000235:genetics; D006160:Guanosine Triphosphate / Q000378:metabolism; D006367:HeLa Cells; D006801:Humans; D007438:Introns; D007527:Isoenzymes / Q000235:genetics / Q000378:metabolism; D008969:Molecular Sequence Data; D065636:Myotonin-Protein Kinase; D011485:Protein Binding; D017346:Protein Serine-Threonine Kinases / Q000235:genetics* / Q000378:metabolism; D011505:Protein-Tyrosine Kinases / Q000235:genetics / Q000378:metabolism; D051381:Rats; D017422:Sequence Analysis, DNA; D020764:cdc42 GTP-Binding Protein / Q000378:metabolism*
D020413:3' Untranslated Regions; C585517:DMPK protein, human; D007527:Isoenzymes; D006160:Guanosine Triphosphate; D004247:DNA; C118666:CDC42BPB protein, human; D011505:Protein-Tyrosine Kinases; D065636:Myotonin-Protein Kinase; D017346:Protein Serine-Threonine Kinases; D020764:cdc42 GTP-Binding Protein