baboon: Biological Overview | Evolutionary Homologs | Regulation | Developmental Biology | Effects of Mutation | References

Gene name - baboon

Synonyms - Atr-I

Cytological map position - 45A1--45A2

Function - receptor tyrosine kinase

Keywords - TGFbeta/activin signaling,
cell proliferation

Symbol - babo

FlyBase ID:FBgn0011300

Genetic map position - 2-[58]

Classification - Type 1 activin-A-receptor

Cellular location - cell surface, transmembrane

NCBI links: | Entrez Gene |
Recent literature
Song, W., Cheng, D., Hong, S., Sappe, B., Hu, Y., Wei, N., Zhu, C., O'Connor, M. B., Pissios, P. and Perrimon, N. (2017). Midgut-derived Activin regulates glucagon-like action in the fat body and glycemic control. Cell Metab 25(2): 386-399. PubMed ID: 28178568
While high-caloric diet impairs insulin response to cause hyperglycemia, whether and how counter-regulatory hormones are modulated by high-caloric diet is largely unknown. This study found that enhanced response of Drosophila adipokinetic hormone (AKH, the glucagon homolog) in the fat body is essential for hyperglycemia associated with a chronic high-sugar diet. The activin type I receptor Baboon (Babo) autonomously increases AKH signaling without affecting insulin signaling in the fat body via, at least, increase of Akh receptor (AkhR) expression. Further, it was demonstrated that Activin-β (Acβ), an activin ligand predominantly produced in the enteroendocrine cells (EEs) of the midgut, is upregulated by chronic high-sugar diet and signals through Babo to promote AKH action in the fat body, leading to hyperglycemia. Importantly, activin signaling in mouse primary hepatocytes also increases glucagon response and glucagon-induced glucose production, indicating a conserved role for activin in enhancing AKH/glucagon signaling and glycemic control.
Wang, Z., Lee, G., Vuong, R. and Park, J. H. (2019). Two-factor specification of apoptosis: TGF-beta signaling acts cooperatively with ecdysone signaling to induce cell- and stage-specific apoptosis of larval neurons during metamorphosis in Drosophila melanogaster. Apoptosis 24(11-12): 972-989. PubMed ID: 31641960
Developmentally regulated programmed cell death (PCD) is one of the key cellular events for precise controlling of neuronal population during postembryonic development of the central nervous system. Previous work has shown that a group of corazonin-producing peptidergic neurons (vCrz) undergo apoptosis in response to ecdysone signaling via ecdysone receptor (EcR)-B isoforms and Ultraspiracle during early phase of metamorphosis. Further utilizing genetic, transgenic, and mosaic analyses, it was found that TGF-beta signaling mediated by a glia-produced ligand, Myoglianin, type-I receptor Baboon (particularly Babo-A isoform) and dSmad2, is also required autonomously for PCD of the vCrz neurons. These studies show that TGF-beta signaling is not acting epistatically to EcR or vice versa. It was also shown that ectopic expression of a constitutively active phosphomimetic form of dSmad2 (dSmad2(PM)) is capable of inducing premature death of vCrz neurons in larva but not other larval neurons. Intriguingly, the dSmad2(PM)-mediated killing is completely suppressed by coexpression of a dominant-negative form of EcR (EcR(DN)), suggesting that EcR function is required for the proapoptotic dSmad2(PM) function. Based on these data, it is suggested that TGF-beta and ecdysone signaling pathways act cooperatively to induce vCrz neuronal PCD. It is proposed that this type of two-factor authentication is a key developmental strategy to ensure the timely PCD of specific larval neurons during metamorphosis.
Lai, Y. W., Chu, S. Y., Li, J. C., Chen, P. L., Chen, C. H. and Yu, H. H. (2020). Visualization of Endogenous Type I TGF-beta Receptor Baboon in the Drosophila Brain. Sci Rep 10(1): 5132. PubMed ID: 32198477
The transforming growth factor beta (TGF-beta) signaling pathway is evolutionarily conserved and widely used in the animal kingdom to regulate diverse developmental processes. Prior studies have shown that Baboon (Babo), a Drosophila type I TGF-beta receptor, plays essential roles in brain development and neural circuit formation. However, the expression pattern for Babo in the developing brain has not been previously reported. This study generated a knock-in fly with a human influenza hemagglutinin (HA) tag at the C-terminus of Babo and assessed its localization. Babo::HA was primarily expressed in brain structures enriched with neurites, including the mushroom body lobe and neuropils of the optic lobe, where Babo has been shown to instruct neuronal morphogenesis. Since the babo 3' untranslated region contains a predicted microRNA-34 (miR-34) target sequence, tests were performed to see whether Babo::HA expression was affected by modulating the level of miR-34. Babo was found to be upregulated by mir-34 deletion and downregulated by miR-34 overexpression, confirming that it is indeed a miR-34 target gene. Taken together, these results demonstrate that the babo(HA) fly permits accurate visualization of endogenous Babo expression during brain development and the construction of functional neural circuits.
Lai, Y. W., Chu, S. Y., Li, J. C., Chen, P. L., Chen, C. H. and Yu, H. H. (2020). Visualization of Endogenous Type I TGF-beta Receptor Baboon in the Drosophila Brain. Sci Rep 10(1): 5132. PubMed ID: 32198477
The transforming growth factor beta (TGF-beta) signaling pathway is evolutionarily conserved and widely used in the animal kingdom to regulate diverse developmental processes. Prior studies have shown that Baboon (Babo), a Drosophila type I TGF-beta receptor, plays essential roles in brain development and neural circuit formation. However, the expression pattern for Babo in the developing brain has not been previously reported. This study generated a knock-in fly with a human influenza hemagglutinin (HA) tag at the C-terminus of Babo and assessed its localization. Babo::HA was primarily expressed in brain structures enriched with neurites, including the mushroom body lobe and neuropils of the optic lobe, where Babo has been shown to instruct neuronal morphogenesis. Since the babo 3' untranslated region contains a predicted microRNA-34 (miR-34) target sequence, tests were performed to see whether Babo::HA expression was affected by modulating the level of miR-34. Babo was found to be upregulated by mir-34 deletion and downregulated by miR-34 overexpression, confirming that it is indeed a miR-34 target gene. Taken together, these results demonstrate that the babo(HA) fly permits accurate visualization of endogenous Babo expression during brain development and the construction of functional neural circuits.

Although there is compelling proof for the existence of invertebrate BMP-like signaling pathways, the evidence for invertebrate TGF-beta or Activin-like signaling pathways has been scant. Baboon (Babo) is an invertebrate Activin type I receptor: the characterization of Baboon may well be the first evidence for the existence of an Activin-like signaling pathway in Drosophila. Null mutations and germ-line clonal analysis demonstrate that babo is not required during embryogenesis but is essential for proper pupation and adult viability. Loss of babo function results in late larval or early pupal lethality. The major defect in these mutants is a reduction of cell proliferation within the primordia for adult structures, specifically imaginal discs and brain tissue. Activated Babo can signal to vertebrate TGF-beta/Activin, but not to BMP-responsive promoters in cell culture. Activated Babo cannot bind to or interact with Drosophila Mad in tissue culture but can utilize a new Drosophila Smad homolog, dSmad2 (Smad on X), which relates most closely to the vertebrate Smads 2 and 3. Drosophila dSmad2 is highly expressed in tissues that require babo function and can be phosphorylated by either overexpression of activated Babo or by overexpression of wild-type Punt and Babo together. On the basis of these results, it is proposed that an Activin-like signaling pathway exists in Drosophila, which is required for proper cell proliferation in many primordial adult tissues (Brummel, 1999).

Upon cloning of Baboon, it was first necessary to test whether the newly identified receptor acted as a receptor for the known BMP-type ligands in Drosophila. The reduced size of imaginal discs and brain tissue is not unique to babo mutations: this is also a characteristic feature of mutations in Drosophila BMP signaling pathways. In the embryo, all three characterized BMP ligands, Decapentaplegic (Dpp), Screw (Scw), and Glass bottom boat (Gbb), participate in specific developmental processes. Because Scw and Dpp are both critically important for formation of the amnioserosa tissue at the blastoderm stage, a Kruppel-lacZ line was used to follow the fate of amnioserosa tissue in babo mutants: such tissue was found to be unaffected. The role of Babo in midgut development was analyzed. Between stages 14 and 16, three constrictions form in the midgut producing a four-chambered vessel. Dpp is required for formation of the second midgut constriction, whereas gbb mutants lack the first constriction. Mutant embryos derived from babo germ-line clones exhibit a normal four-chambered midgut at stage 16. Furthermore, visceral mesoderm expression of the Gbb target gene Antennapedia, and the Dpp target gene Ubx, are both normal in babo mutants. In addition to these activities, both Dpp and Gbb are required for growth and patterning of imaginal discs and larval brains. Therefore, the expression of several target genes was examined in babo mutant discs. In wild-type discs, the genes optomotor blind (omb) and spalt (sal) respond to Dpp in a dose-dependent fashion. In addition, proper omb expression also requires input from the Gbb ligand. In leg discs, Dpp represses wg in the ventral portion of the disc. No alterations were found in the expression patterns of omb, sal, and wg in any babo mutant disc. These results indicate that babo does not likely function as a receptor for Dpp, Scw, or Gbb during Drosophila development (Brummel, 1999).

Clonal analysis of babo mutants as well as overexpression of constitutively activated Babo receptors was carried out to identify the developmental function of Babo. The results suggest that Babo primarily regulates cell proliferation and has only minimal affects on patterning. The consequences of expressing a constitutively active form of Babo (Babo*, Q302D) in imaginal discs via the UAS-Gal4 system was examined. Ubiquitous expression of the constitutively active receptor leads to tissue overgrowth in the wing, but only limited pattern abnormalities. Surface area measurements indicate an ~30% increase in wing size for a particular UAS-Babo* line. To determine whether this increase in wing surface area results from an increase in cell size or cell number, wing hairs (single apical extensions found on the surface of each wing blade cell) were counted within a fixed area at two locations on the dorsal surface of the wing. An ~20% increase in the density of cells at both positions was found, as compared with control flies. Assuming that there is no decrease in cell death, and taking into account the ~30% increase in wing size, these results suggest that one of every two cells undergoes an extra round of division during wing formation as a result of ectopically activated Babo expression (Brummel, 1999).

Because genetic data indicate that in Drosophila Babo is not a component of Dpp signaling, the specificity of Babo activity was examined in mammalian cell culture assays using several different pathway specific promoters. Using a TGF-beta/Activin responsive promoter, p3TP, fused to luciferase, cultured cells were cotransfected with the reporter alone or with wild-type forms of Babo or the mammalian TGFbeta type-I receptor, TbetaRI. In the absence of TGF-beta, only basal levels of luciferase activity are observed. Addition of TGF-beta or transfection with an activated TbetaRI results in a strong induction of the tagged promoter. A similar induction is observed when the constitutively active form of Babo is cotransfected with the tagged promoter. In contrast, cotransfection with the constitutively active Dpp receptor Tkv does not stimulate the TGF-beta/Activin responsive reporter. Similar results were obtained with a second Activin/TGF-beta responsive element (known as ARE). Cotransfection of cultured cells with the second tagged promoter and activated Babo results in a fivefold induction in luciferase activity. This stimulation is similar to levels of induction produced by the activated forms of mammalian receptors TbetaRI or ActRIB. Tkv fails to modulate induction of the second TGF-beta/Activin responsive promoter. Together these data indicate that Babo specifically activates a TGF/Activin-like pathway in mammalian cells and suggest that this receptor may regulate a Smad2/Smad3-like pathway in Drosophila (Brummel, 1999).

Baboon was shown to function through the newly identified dSmad2, a Drosophila homolog of mammalian Smad2 and Smad3, which function in Activin signaling. Activated Babo induces phosphorylation on the last two serines of dSmad2. These data suggest that dSmad2 is a downstream target of Babo and is phosphorylated on the last two serine residues in the carboxyl terminus. Babo-dependent phosphorylation of dSmad2 also induces association with Medea, a homolog of mammalian Smad4. Phosphorylation of dSmad2 on the last two serines is necessary for receptor-dependent induction of heteromeric complexes of dSmad2 and Medea. Mammalian Activin receptors require dimerization with a type II receptor for their function. Punt, the Drosophila type II receptor was shown to function to activate Babo. dSmad2 interacts transiently and specifically with Punt-Babo receptor complexes. Taken together, these functional and biochemical analyses strongly suggest that dSmad2 is a Drosophila homolog of Smad2/Smad3 and functions as a downstream signaling component that directly interacts with Babo (Brummel, 1999).

The simplicity of the babo loss-of-function phenotype in Drosophila is striking in light of the number of speculated roles for Activin signaling in vertebrates. In particular, the fact that babo loss-of-function mutations primarily affects cell growth and proliferation in late development, but not cell fate specification or patterning processes, stands in marked contrast to the situation in vertebrates in which Activin or Activin-like signaling pathways have been implicated in a wide range of early developmental events, as well as adult functions such as reproductive potential. Similarly, in Drosophila the BMP-like factor Dpp has been implicated in the control of cell fate, cell proliferation, and patterning processes. Thus, the Babo signaling pathway appears to be unique in that it seems to act primarily in only one of these interconnected processes. It should be recognized, however, that Babo signaling may contribute to some patterning processes and/or cell fate decisions. For example, in the brain, it has yet to be determined whether all of the morphological defects can be accounted for by reduced proliferation rates of certain neuroblast populations or whether there are also changes in cell fate specification. Likewise, the cause of the enlarged anal pads, observed in babo mutants, during larval development has not been investigated. As the anal organ is involved in regulating salt homeostasis in insects, the enlarged anal pads might simply represent swelling due to a salt imbalance or the inability to regulate water content. Larvae missing babo function also fail to exhibit a typical behavioral trait, which is to move away from moist food before pupation. Thus, the inability to assess hydration as the result of abnormal brain development may underlie both the enlarged anal pads and the failure to seek a drier climate for pupation (Brummel, 1999).

The Babo pathway appears to act in a positive manner to stimulate cell proliferation. How might Babo signaling couple to cell proliferation? Recent analysis of cell growth and division in the Drosophila wing imaginal discs has led to the conclusion that the cell division rate is normally coupled to increases in cell mass such that a relatively constant ratio between the two processes is maintained (Neufeld, 1998). Because mutations that affect protein synthesis, such as Minutes, retard cell proliferation without changing cell size, Neufeld favored a model in which tissue growth is upstream and dominant to cell cycle control. Consistent with this view, it was found that if the cell cycle is artificially stimulated to give a higher division rate, then the size of the cells decreases. Conversely, if mitosis in the wing is blocked by inactivation of the Drosophila cdc2 kinase, then wings of normal size are produced but they contain smaller numbers of larger cells (Weigmann, 1997). Overexpression of activated Babo in the wing appears to alter the process that couples growth and proliferation rates with the determination of tissue size. The simplest explanation for these results is that Babo signaling stimulates some aspect of the cell cycle resulting in an increased proliferation rate and reduced cell size similar to that described by Neufeld. However, the fact that larger wings are seen despite the smaller cell size suggests that Babo may independently affect tissue growth parameters as well as the cell cycle. Therefore, additional studies on the mechanism of Babo signaling could help reveal how cell growth and proliferation are linked to the determination of final tissue size (Brummel, 1999).

TGF-β signals regulate axonal development through distinct Smad-independent mechanisms

Proper nerve connections form when growing axons terminate at the correct postsynaptic target. Transforming growth factor β (TGFβ) signals regulate axon growth. In most contexts, TGFβ signals are tightly linked to Smad transcriptional activity. Although known to exist, how Smad-independent pathways mediate TGFβ responses in vivo is unclear. In Drosophila mushroom body (MB) neurons, loss of the TGFβ receptor Baboon (Babo) results in axon overextension. Conversely, misexpression of constitutively active Babo results in premature axon termination. Smad activity is not required for these phenotypes. This study shows that Babo signals require the Rho GTPases Rho1 and Rac, and LIM kinase1 (LIMK1), which regulate the actin cytoskeleton. Contrary to the well-established receptor activation model, in which type 1 receptors act downstream of type 2 receptors, this study shows that the type 2 receptors Wishful thinking (Wit) and Punt act downstream of the Babo type 1 receptor. Wit and Punt regulate axon growth independently, and interchangeably, through LIMK1-dependent and -independent mechanisms. Thus, novel TGFβ receptor interactions control non-Smad signals and regulate multiple aspects of axonal development in vivo (Ng, 2008).

Once growing axons reach the correct postsynaptic target, axon outgrowth terminates and synaptogenesis begins. These studies suggest that TGFβ signals play a role. When Babo is inactivated, MB axon growth does not terminate properly and overextends across the midline. Consistent with this, CA Babo expression results in precocious termination, forming axon truncations. How Babo is spatially and temporally regulated remains to be determined. Analogous to the Drosophila NMJ, MB axon growth might be terminated through retrograde signalling. Target-derived TGFβ ligands could signal to Babo (on MB axon growth cones) and stop axons growing further. In an alternative scenario, TGFβ ligands might act as a positional cue that prevents MB axons from crossing the midline. Recent data have shown that Babo acting through Smad2 restricts individual R7 photoreceptor axons to single termini. Loss of Babo, Smad2, or the nuclear import regulator Importin α3 (Karyopherin α3 - FlyBase), results in R7 mutant axons invading neighbouring R7 terminal zones. With the phenotype described in this study, Babo could similarly be restricting MB axons to appropriate termination zones, its loss resulting in inappropriate terminations on the contralateral side (Ng, 2008).

In contrast to MB neurons, Babo inactivation in AL and OL neurons resulted in axon extension and targeting defects. This might reflect cell-intrinsic differences in the response in different neurons to a common Babo signalling program. This may be the case for MB axon pruning and DC axon extension, which require Babo/Smad2 signals. Whether these differences derive from cell-intrinsic properties, or from Babo signal transduction, they underline the importance of Smad-independent signals in many aspects of axonal development (Ng, 2008).

The results suggest that Smad-independent signals involve Rho GTPases. One caveat in genetic interaction experiments is that the loss of any given gene might not be dosage-sensitive with a particular assay. Nevertheless, all the manipulations together suggest that Babo-regulated axon growth requires Rho1, Rac and LIMK1. How Babo signals involve Rho GTPases remains to be fully determined. In addition to LIMK1, which binds to Wit, one possibility, as demonstrated for many axon guidance receptors, is that the RhoGEFs, RhoGAPs and Rho proteins might be linked to the Babo receptor complex. Thus, ligand-mediated changes in receptor properties would lead to spatiotemporal changes in Rho GTPase and LIMK1 activities (Ng, 2008).

The data suggest that a RhoGEF2/Rho1/Rok/LIMK1 pathway mediates Babo responses. Whether Rac activators are required is unclear, as tested RacGEFs do not genetically interact with babo. In this respect, rather than through GEFs, Babo might regulate Rac through GAPs, by inhibiting Tumbleweed (Tum) activity (Ng, 2008).

Do mutations in Rho1 and Rac components phenocopy babo phenotypes? β lobe overextensions are observed in Rok, Rho1 and Rac mutant neurons. In MB neurons, Rac GTPases also control axon outgrowth, guidance and branching. Rho1 also has additional roles in MB neurons. Although Rho1 mutant neuroblasts have cell proliferation defects, single-cell αβ clones do show β lobe extensions. RhoGEF2 strong loss-of-function clones do not exhibit axon overextension. As there are 23 RhoGEFs in the Drosophila genome, there might well be redundancy in the way Rho1 is activated. LIMK1 inactivation in MB neurons was reported previously. Axon overextensions were not observed as LIMK1 loss results in axon outgrowth and misguidance phenotypes. This suggests that LIMK1 mediates multiple axon guidance signals, of which TGFβ is a subset in MB morphogenesis (Ng, 2008).

Although their phenotypes are similar, several lines of evidence indicate that CA Babo does not simply reflect LIMK1 misregulation in MB neurons. First, whereas LIMK1 genetically interacts with most Rho family members and many Rho regulators, CA babo is dosage-sensitive only to Rho1 and Rac and specific Rho regulators, suggesting that Babo regulates LIMK1 only through a subset of Rho signals (Ng, 2008).

Second, the LIMK1 misexpression phenotype is suppressed by expression of wild-type cofilin (Twinstar Tsr), S3A Tsr, or the cofilin phosphatase Slingshot (Ssh). By contrast, only wild-type Tsr, but not S3A Tsr or Ssh, suppresses CA Babo. The suppression by wild-type Tsr might reflect a restoration of the endogenous balance or spatial distribution of cofilin-on (unphosphorylated) and -off (phosphorylated) states within neurons. Indeed, optimal axon outgrowth requires cofilin to undergo cycles of phosphorylation and dephosphorylation. Since S3A forms of cofilin cannot be inactivated and recycled from actin-bound complexes, wild-type cofilin is more potent in actin cytoskeletal regulation (Ng, 2008).

CA Babo might not simply misregulate LIMK1 but also additional cofilin regulators. Recent data suggest that extracellular cues (including mammalian BMPs) can regulate cofilin through Ssh phosphatase and phospholipase Cγ activities. In different cell types, cofilin phosphorylation and phospholipid binding (which also inhibits cofilin activity) states vary and potently affect cell motility and cytoskeletal regulation. Whether a combination of LIMK1, Ssh and phospholipid regulation affects cofilin-dependent axon growth remains to be determined (Ng, 2008).

Third, by phalloidin staining, LIMK1, but not CA Babo, misexpression results in a dramatic increase in F-actin in MB neurons. Thus, CA Babo does not in itself lead to actin misregulation. Fourth, Babo also regulates axon growth independently of LIMK1 (Ng, 2008).

This study differs significantly from the canonical model of Smad signalling, in which type 1 receptors function downstream of the ligand-type 2 receptor complex. In this study, the gain- and loss-of-function results suggest that type 2 receptors act downstream of type 1 signals. Since ectopic only Wit and Put suppress the babo axon overextension phenotype, this implies that Smad-dependent and -independent signals have distinct type 1/type 2 receptor interactions. How these interactions propagate Smad-independent signals remains to be fully determined. Babo could act as a ligand-binding co-receptor with Wit and Put. In addition, Babo kinase activity could regulate type 2 receptor or Rho functions. The results suggest, however, that provided that Wit or Put signals are sufficiently high, Babo is not required. Whatever the mechanism(s), it is likely that Babo requires the Wit C-terminus-LIMK1 interaction to relay cofilin phosphoregulatory signals. How Put functions is unclear. Since the put135 allele (used in this study) carries a missense mutation within the kinase domain, this suggests that kinase activity is essential. put does not genetically interact with LIMK1. Since Put lacks the C-terminal extension of Wit that is necessary for LIMK1 binding, this suggests that Put acts independently of LIMK1. One potential effector is Rac, which, in the context of Babo signalling, also appears to be Pak1- and thus LIMK1-independent (Ng, 2008).

In MB neurons, Wit and Put can function interchangeably. In other in vivo paradigms, type 2 receptors are not interchangeable. However, since the Wit C-terminal tail is required to substitute for Put, this suggests that Wit axon growth signals are independent of its kinase activity. Together, this suggests that Smad-independent signals involve LIMK1-dependent and -independent mechanisms (Ng, 2008).

This study shows that Babo mediates two distinct responses in related MB populations. How do MB neurons choose between axon pruning and axon growth? The babo rescue studies suggest that whereas Baboa or Babob elicits Smad-independent responses, only Baboa mediates Smad-dependent responses. Since Babo isoforms differ only in the extracellular domain, differences in ligand binding could determine Smad2 or Rho GTPase activation. However, it is worth noting that in DC neurons, either isoform mediates axon extension through Smad2 and Medea. In addition, although expressed in all MB neurons, CA babo misexpression (which confers ligand-independent signals) perturbs only αβ axons. Thus, cell-intrinsic properties might also be essential in determining Babo responses (Ng, 2008).

Many TGFβ ligands signal through Babo. For example, Dawdle, an Activin-related ligand, patterns Drosophila motor axons, whereas Activin (Activin-β, FlyBase) is required for MB axon pruning. Whether these ligands regulate Babo MB, AL and OL axonal morphogenesis is unclear. Taken together, the evidence suggests that Babo signalling is varied in vivo and is involved in many aspects of neuronal development (Ng, 2008).

TGFβ signals are responsible for many aspects of development and disease and, throughout different models, Smad pathways are closely involved. Although Smad-independent pathways are known, their mechanisms and roles in vivo are unclear. TGFβ signals often drive cell shape changes in vivo. During epithelial-to-mesenchymal transition (EMT), cells lose their epithelial structure and adopt a fibroblast-like structure that is essential for cell migration during development and tumour invasion. TGFβ-mediated changes in the actin cytoskeleton and adherens junctions are necessary for EMT. Although Smads are crucial, TGFβ signals also involve the Cdc42-Par6 complex, resulting in cell de-adhesion and F-actin breakdown through Rho1 degradation. In other studies, however, TGFβ-mediated EMT has been shown to require Rho1, which can be regulated by Smad activity (Ng, 2008).

Many TGFβ-driven events in Drosophila are Smad-dependent. Whether Smad-independent roles exist beyond those identified in this study remains to be tested. This study therefore provides a framework to understand how non-Smad signals regulate cell morphogenesis during development (Ng, 2008).


Both BABO transcripts are encoded within a 9-kb genomic fragment and contain seven exons with exon 3a/b being differentially spliced to produce the two isoforms (Brummel, 1999)

Transcript sizes - 3.6, 4.0 and 4.9-kb

Number of exons - 7


Amino Acids - 601

Structural Domains

A transmembrane protein serine/threonine kinase, Baboon, that is structurally related to receptors for members of the transforming growth factor-beta (TGF-beta) family has been cloned from Drosophila. The spacing of extracellular cysteines and the cytoplasmic kinase domain of Baboon resemble most closely those of the recently described mammalian type I receptors for TGF-beta and activin. The kinase domain of Baboon bears a 60% to 72% amino acid identity to mammalian type I receptors. The Baboon kinase domain is more distantly related (37% to 40% amino acid sequence identity) to those of the type II receptors, including Drosophila Punt. The extracellular domain of Baboon shows little sequence similarity to other receptors and is larger than those of serine/threonine kinase receptors from vertebrates. The spacing of the 10 extracellular cysteines in Baboon resembles the spacing in the other type I receptors, and includes the cysteine box motif near the transmembrane region that is characteristic of the serine/threonine kinase receptor family. Comparison of Baboon with other type I receptors reveals the presence of a characteristic 30-amino-acid domain immediately upstream of the kinase region in all these receptors. This domain, of unknown function, contains a repeated Gly-Ser sequence and is therefore referred to as the GS domain. Two alternative forms of Baboon have been identified that differ in an ectodomain region encompassing the cysteine box motif characteristic of receptors in this family. The second class of cDNA is represented by one clone of 4.9 kb encoding a product in which a 70-amino-acid sequence replaces a 49-amino-acid sequence in the extracellular region near the transmembrane domain. Aside from the cysteine box, which is partially included in this region, there is virtually no similarity between the two alternative sequences. The larger size of Baboon compared with mammalian type I receptor (Baboon contains a 94 amino acid N-terminal region that is not present in the mammalian proteins) correlates with the presence of a large extracellular region and more N-linked glycosylation sites in Baboon (Wrana, 1994).

baboon: Evolutionary Homologs | Regulation | Developmental Biology | Effects of Mutation | References

date revised: 21 January 99

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