Hgs (Hrs), a FYVE domain protein, is involved in Smad signaling through cooperation with SARA.
Smad proteins are effector molecules that transmit signals from the receptors for the transforming growth factor beta (TGF-beta) superfamily to the nucleus; of the Smad proteins, Smad2 and Smad4 are essential components for mouse early embryogenesis. We demonstrated that Hgs, a FYVE domain protein, binds to Smad2 in its C-terminal half and cooperates with another FYVE domain protein, the Smad anchor for receptor activation (SARA), to stimulate activin receptor-mediated signaling through efficient recruitment of Smad2 to the receptor. Furthermore, a LacZ knock-in allele of the C-terminal half-deletion mutant of mouse Hgs was created by gene targeting. The introduced mutation causes an embryonic lethality between embryonic days 8.5 and 10.5. Mutant cells showed significantly decreased responses to stimulation with activin and TGF-beta. These findings suggest that the two FYVE domain proteins, Hgs and SARA, are prerequisites for receptor-mediated activation of Smad2.
Miura
S
S
Department of Microbiology and Immunology, Tohoku University School of Medicine, Aoba-ku, Japan.
Takeshita
T
T
Asao
H
H
Kimura
Y
Y
Murata
K
K
Sasaki
Y
Y
Hanai
J I
JI
Beppu
H
H
Tsukazaki
T
T
Wrana
J L
JL
Miyazono
K
K
Sugamura
K
K
D029404:Activin Receptors; D028341:Activins; D000818:Animals; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism*; D002454:Cell Differentiation; D002460:Cell Line; D002678:Chimera / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D004622:Embryo, Mammalian / Q000033:anatomy & histology / Q000502:physiology; D056827:Endosomal Sorting Complexes Required for Transport; D018390:Gene Targeting; D017930:Genes, Reporter / Q000187:drug effects; D007265:Inhibins / Q000494:pharmacology; D046911:Macromolecular Substances; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic / Q000033:anatomy & histology / Q000235:genetics / Q000378:metabolism; D010750:Phosphoproteins / Q000235:genetics / Q000378:metabolism*; D010766:Phosphorylation; D011233:Precipitin Tests; D017978:Receptors, Growth Factor / Q000378:metabolism*; D015398:Signal Transduction; D051899:Smad2 Protein; D051900:Smad3 Protein; D015534:Trans-Activators / Q000235:genetics / Q000378:metabolism*; D016212:Transforming Growth Factor beta / Q000494:pharmacology
D002352:Carrier Proteins; D004268:DNA-Binding Proteins; D056827:Endosomal Sorting Complexes Required for Transport; D046911:Macromolecular Substances; D010750:Phosphoproteins; D017978:Receptors, Growth Factor; D051899:Smad2 Protein; C497783:Smad2 protein, mouse; D051900:Smad3 Protein; C497791:Smad3 protein, mouse; D015534:Trans-Activators; D016212:Transforming Growth Factor beta; C096164:hepatocyte growth factor-regulated tyrosine kinase substrate; D028341:Activins; D007265:Inhibins; D029404:Activin Receptors