Roles of gamma-carboxylation and a sex hormone-binding globulin-like domain in receptor-binding and in biological activities of Gas6.
Gas6 is a ligand for an Axl/Sky receptor tyrosine kinase subfamily and has a structure composed of a Gla domain, four EGF-like domains and a C-terminal sex hormone-binding globulin (SHBG)-like domain. When examining the role of each domain in receptor-binding and biological activities of Gas6, we found that receptor-binding and mitogenic activities were markedly reduced by inhibiting gamma-carboxylation of the Gla domain, while a Gas6 mutant composed of only an SHBG-like domain retained both of these activities. Thus, the SHBG-like domain is apparently an entity indispensable for Gas6 activities, and gamma-carboxylation of the Gla domain has a regulatory role in retaining the activity of native Gas6.
Tanabe
K
K
Department of Biology, Faculty of Science, Kyushu University, Higashi-ku, Fukuoka, Japan.
Nagata
K
K
Ohashi
K
K
Nakano
T
T
Arita
H
H
Mizuno
K
K
D016475:3T3 Cells; D000818:Animals; D001483:Base Sequence; D001665:Binding Sites; D001921:Brain / Q000378:metabolism; D016466:CHO Cells; D002455:Cell Division / Q000187:drug effects; D006224:Cricetinae; D004247:DNA / Q000096:biosynthesis; D018076:DNA, Complementary; D036341:Intercellular Signaling Peptides and Proteins; D007700:Kinetics; D008024:Ligands; D051379:Mice; D008961:Models, Structural; D008969:Molecular Sequence Data; D016254:Mutagenesis, Insertional; D009838:Oligodeoxyribonucleotides; D015513:Oncogene Proteins / Q000378:metabolism; D011506:Proteins / Q000737:chemistry* / Q000378:metabolism* / Q000494:pharmacology; D011518:Proto-Oncogene Proteins; D051381:Rats; D020794:Receptor Protein-Tyrosine Kinases / Q000378:metabolism; D011993:Recombinant Fusion Proteins / Q000378:metabolism; D011994:Recombinant Proteins / Q000737:chemistry / Q000378:metabolism; D012738:Sex Hormone-Binding Globulin / Q000737:chemistry* / Q000378:metabolism; D000094963:Axl Receptor Tyrosine Kinase; D000099255:Growth Arrest-Specific Protein 6
D004247:DNA; D018076:DNA, Complementary; D036341:Intercellular Signaling Peptides and Proteins; D008024:Ligands; D009838:Oligodeoxyribonucleotides; D015513:Oncogene Proteins; D011506:Proteins; D011518:Proto-Oncogene Proteins; D020794:Receptor Protein-Tyrosine Kinases; D011993:Recombinant Fusion Proteins; D011994:Recombinant Proteins; D012738:Sex Hormone-Binding Globulin; D000094963:Axl Receptor Tyrosine Kinase; D000099255:Growth Arrest-Specific Protein 6; C084944:TYRO3 protein, human