XIAP, a cellular member of the inhibitor of apoptosis protein family, links the receptors to TAB1-TAK1 in the BMP signaling pathway.
Signals elicited by transforming growth factor-beta (TGF-beta) superfamily ligands are generated following the formation of heteromeric receptor complexes consisting of type I and type II receptors. TAK1, a member of the MAP kinase kinase kinase family, and its activator, TAB1, participate in the bone morphogenetic protein (BMP) signaling pathway involved in mesoderm induction and patterning in early Xenopus embryos. However, the events leading from receptor activation to TAK1 activation remain to be identified. A yeast interaction screen was used to search for proteins that function in the pathway linking the receptors and TAB1-TAK1. The human X-chromosome-linked inhibitor of apoptosis protein (XIAP) was isolated as a TAB1-binding protein. XIAP associated not only with TAB1 but also with the BMP receptors in mammalian cells. Injection of XIAP mRNA into dorsal blastomeres enhanced the ventralization of Xenopus embryos in a TAB1-TAK1-dependent manner. Furthermore, a truncated form of XIAP lacking the TAB1-binding domain partially blocked the expression of ventral mesodermal marker genes induced by a constitutively active BMP type I receptor. These results suggest that XIAP participates in the BMP signaling pathway as a positive regulator linking the BMP receptors and TAB1-TAK1.
Yamaguchi
K
K
Department of Molecular Biology, Graduate School of Science, Nagoya University, Nagoya, Japan.
Nagai
S
S
Ninomiya-Tsuji
J
J
Nishita
M
M
Tamai
K
K
Irie
K
K
Ueno
N
N
Nishida
E
E
Shibuya
H
H
Matsumoto
K
K
D048868:Adaptor Proteins, Signal Transducing; D000595:Amino Acid Sequence; D000818:Animals; D017209:Apoptosis / Q000502:physiology*; D001665:Binding Sites / Q000235:genetics; D052004:Bone Morphogenetic Protein Receptors; D019485:Bone Morphogenetic Proteins / Q000502:physiology*; D002352:Carrier Proteins / Q000502:physiology*; D018507:Gene Expression Regulation, Developmental; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins; D020930:MAP Kinase Kinase Kinases; D010749:Phosphoprotein Phosphatases; D017346:Protein Serine-Threonine Kinases / Q000502:physiology*; D011506:Proteins / Q000235:genetics / Q000502:physiology*; D011956:Receptors, Cell Surface / Q000502:physiology; D017978:Receptors, Growth Factor; D011987:Receptors, Steroid / Q000502:physiology; D011988:Receptors, Thyroid Hormone / Q000502:physiology; D012441:Saccharomyces cerevisiae / Q000235:genetics; D017384:Sequence Deletion; D015398:Signal Transduction; D051636:X-Linked Inhibitor of Apoptosis Protein; D014981:Xenopus; D029867:Xenopus Proteins; D000099151:MAP Kinase Kinase Kinase 7
D048868:Adaptor Proteins, Signal Transducing; D052004:Bone Morphogenetic Protein Receptors; D019485:Bone Morphogenetic Proteins; D002352:Carrier Proteins; D047908:Intracellular Signaling Peptides and Proteins; D020930:MAP Kinase Kinase Kinases; D010749:Phosphoprotein Phosphatases; D017346:Protein Serine-Threonine Kinases; D011506:Proteins; D011956:Receptors, Cell Surface; D017978:Receptors, Growth Factor; D011987:Receptors, Steroid; D011988:Receptors, Thyroid Hormone; D051636:X-Linked Inhibitor of Apoptosis Protein; D029867:Xenopus Proteins; D000099151:MAP Kinase Kinase Kinase 7; C490515:NR2C2 protein, human; C099510:TAB1 protein, MAPKKK activator, vertebrate; C486300:TAB1 protein, human; C496866:XIAP protein, human; C486301:TAB1 protein, Xenopus