Human talus bones from the Middle Pleistocene site of Sima de los Huesos (Sierra de Atapuerca,Burgos, Spain)

Here we present and describe comparatively 25 talus bones from the Middle Pleistocene site of the Sima de los Huesos (SH) (Sierra de Atapuerca, Burgos, Spain). These tali belong to 14 individuals (11 adult and three immature). Although variation among Middle and Late Pleistocene tali tends to be subtle, this study has identified unique morphological characteristics of the SH tali. They are vertically shorter than those of Late Pleistocene Homo sapiens, and show a shorter head and a broader lateral malleolar facet than all of the samples. Moreover, a few shared characters with Neanderthals are consistent with the hypothesis that the SH population and Neanderthals are sister groups. These shared characters are a broad lateral malleolar facet, a trochlear height intermediate between modern humans and Late Pleistocene H. sapiens, and a short middle calcaneal facet. It has been possible to propose sex assignment for the SH tali based on their size. Stature estimates based on these fossils give a mean stature of 174.4 cm for males and 161.9 cm for females, similar to that obtained based on the long bones from this same site.     

THE ROLE OF DIATOMS IN STROMATOLITE GROWTH: TWO EXAMPLES FROM MODERN FRESHWATER SETTINGS1

Some modern laminated and calcified stromatolitic structures are partially or completely formed by eukaryotes. Diatom populations in freshwater environments with elevated ionic concentrations contribute to calcite precipitation, and the formation of distinctive mineral-rich stromatolitic laminae. Two types of stromatolite-forming diatom populations were observed. In the first example, in stromatolies growing on a quarry ledge near Laegerdorf, North Germany, calcite crystals with biogenic imprints form around polysaccharide stalks of the diatom Gomphonema olivaceum var. calcarea (Cleve) Cleve-Euler. These individually precipitated crystals eventunally become cemented together in layers, forming rigid, laminated stromatolitic deposits which drape over the quarry ledge. In the second example, in stromatolites forming in a shallow stream near Cuatro Ciénegas, Coahuila, Mexico, diatomaceous laminae also form by the accumulation of carbonate particles in a matrix of diatoms and their extracellular polysaccharide products. These laminae become thick enough to drape over individual stromatolite heads. The diatoms responsible for these deposits are Amphora aff. A. Katii Selva, Nitzschia denticula Grun., and six other species. At Cuatro Ciénegas, in addition to the diatomaceous laminae, carbonate-rich cyanobacterial layers, dominated by two cyanobacterial species with different fabrics and porosities, are also present and contribute substantially to the growth of the stromatolites. In both the Laegerdorf and Cuatro Ciénegas examples, entire stromatolites or thick laminations on stromatolites are built by a small number of diatom species which produce copious amounts of extracellular stalk, gel, and sheath material, a property they share with cyanobacterial stromatolite builders.     

ALGAL LIMESTONES WITH PSEUDOMORPHS AFTER GYPSUM FROM THE MIDDLE JURASSIC OF SCOTLAND

Hudson, J. D.: Algal limestones with pseudomorphs after gypsum from the Middle Jurassic of Scotland. Lethaia , Vol. 3, pp. 11–40. Oslo, January 15th, 1970.
Algal limestones from two horizons within the Great Estuarine Series of the Hebrides are described. That from the Mytilus Shales is a typically stromatolitic limestone formed by algal trapping and binding of micrite pellets. Calcite pseudomorphs after gypsum occur along some of the laminae. The limestones from the Lower Ostrea Beds include less regularly-stromatolitic types, and nodular algal limestones that contain tubes of calcified algae, notably Cayeuxia nodosa Anderson. The algal nodules also yield uncalcified tubes composed of organic material, that are comparable to recent Schizothrix. These algae form inter-growths similar to those recorded from the recent supratidal deposits of the Bahamas. The algal nodules are often coated with microtufa. Pellet- and spheru-lite-limestones are associated with the algae, and pseudomorphs after gypsum are again found. Isotopic data on the carbonate-carbon, and the palaeoecological implications of the algae and the pseudomorphs are discussed.     

THE ROLE OF DIATOMS IN STROMATOLITE GROWTH: TWO EXAMPLES FORM MODERN FRESHWATER SETTINGS1

Some modern laminated find calcified stromatolitic structures are partially or completely formed by eukaryotes. Diatom populations in freshwater environments with elevated ionic concentrations contribute to calcite precipitation, and the formation of distinctive mineral-rich stromatolitic laminae. Two types of stromatolite-forming diatom populations were observed. In the first example, in stromatolites growing on a quarry ledge near Laegerdorf, North Germany, calcite crystals with biogenic imprints form around polysaccharide stalks of the diatom Gomphonema olivaceum var. calcarea (Cleve) Cleve-Euler. These individually precipitated crystals eventually become cemented together in layers, forming rigid, laminated stromatolitic deposits which drape over the quarry ledge. In the second example, in stromatolites forming in a shallow stream near Cuatro Ciénegas, Coahuila, Mexico, diatomaceous laminae also form by the accumulation of carbonate particles in a matrix of diatoms and their extracellular polysaccharide products. These laminae become thick enough to drape over individual stromatolite heads. The diatoms responsible for these deposits are Amphora aff. A. katii Selva, Nitzschia denticula Grun., and six other species. At Cuatro Ciénegas, in addition to the diatomaceous laminae, carbonate-rich cyanobacterial layers, dominated by two cyanobacterial species with different fabrics and porosities, are also present and contribute substantially to the growth of the stromatolites. In both the Laegerdorf and Cuatro Ciénegas examples, entire stromatolites or thick laminations on stromatolites are built by a small number of diatom species which produce copious amounts of extracellular stalk, gel, and sheath material, a propertuy they share with cyanobacterial stromatolite builders.     

Virulence and transmission modes in metapopulations: when group selection increases virulence

Individuals that are infected by a pathogen can transmit it to unrelated conspecifics (horizontal transmission) or to their progeny when they reproduce (vertical transmission). The mechanisms of these two routes of transmission are different and this difference impacts the way virulence evolves in pathogens. More precisely, horizontal transmission depends on the probability that an infected host contacts susceptible conspecifics, and therefore on its lifespan. Vertical transmission additionally depends on the host's fecundity. This additional dependence in vertically transmitted pathogens results in a decrease in their evolutionarily stable (ES) virulence.Spatial structure is another factor that is often supposed to decrease pathogens’ ES virulence, mostly because it impedes competition for transmission in local populations of hosts. In this paper, using the adaptive dynamics framework, we show that spatial structure can increase ES virulence when pathogens are mostly vertically transmitted. This is due to the difference in how pathogens compete for transmission in local population of hosts, depending on how they are transmitted. We also show that symbionts that are horizontally transmitted should respond more to a change in spatial structure than symbionts that are vertically transmitted.     

Effects of localized nitrogen supply treatments on growth and root parameters in Pinus massoniana families under phosphorus deficiency

Aims A heterogeneous spatially distribution of nutrients in natural soil may affect plant growth. The objective of this study was to determine the effects of localized nitrogen (N) supply treatments on growth traits and root parameters among different families in Pinus massoniana.Methods Five families of P. massoniana seedlings from full-sib progenies were used as test materials (1, 25, 49, 52, and 57). This study included two conditions, (i.e. homogeneous phosphorus (P) deficiency vs. heterogeneous P efficiency) among soil layers in combination with four N supply treatments in a one-year pot experiment. These N supply treatments were: (1) Homogeneously high N along the soil profile (HHH); (2) high N-high N-low N (HHL); (3) low N-low N-high N (LLH); (4) low N-low N-on side with N addition and the other side without N supply (LLH/L).Important findings This study indicated that localized N supply treatment did enhance the growth of P. massoniana, and this enhancement mainly happened in the pattern of N applied to deep soil. The results showed: 1) Compared to the homogeneous low P condition, there were increase in the growth traits and root parameters of P. massoniana under heterogeneous low P condition. Particularly, the root length and root surface area under the heterogeneous P deficiency condition were 1.95 times and 2.11 times higher than that subjected to the homogeneous P deficiency. 2) Localized N supply treatment affected seedling growth, and there was a significant interaction among N supply pattern and P condition. In compared with homogeneous N supply treatment, the height, basal diameter and dry weight of seedlings increased significantly by localized N supply treatments (LLH and/or LLH/L) under both two P deficiency conditions. But when the seedlings parameters were enhanced under homogeneous P deficiency, they were inhibited under heterogeneous P deficiency subjected to HHL. 3) Within the two P conditions, LLH and LLH/L stimulated root proliferation significantly, and root parameters were significantly enhanced under the heterogeneous P deficiency condition. Specifically, the root length and root surface area subjected to LLH/L rather than HHH were significantly enhanced by 29.2% and 32.3%, respectively. However, the length and surface area of the roots were suppressed by HHL treatment. 4). There were significant differences in response to different N supply treatments among P. massoniana families Seedlings in the families of 49, 52, and 57 responded to the localized N supply treatments with increased root proliferation, which enhanced seedling dry mass. On the other hand, the seedling growth in the family of 25 were stimulated by N and (or) P concentration, while the response of seedlings in the family of 1 to local nitrogen supply was relatively slow and exhibited growth retardation.     

A New Stromatolitic Mat Builder Discovered from Late Precambrian in Northern China

Abundant and preserved chain algal microfossils have been discovered in cherty stromatolitic mats from the second member of Gaoyuzhuang Formation (about 1,500 Ma old), Ling-qiu county of Shanxi province, China. They are described as Veteronostocale moniliforme Xu et Gao sp. nov.. The small diametral trichomes resemble the Family Nostocaceae in possessing specilized cells resembling the classic heterocysts and akinetes. This paper gives emphasis to the following remark: (1) The Gaoyuzhuang stromatolitic mats were products of microbial (Veteronostocale moniliforme) activity and the plant Nostocaceae was one of the main stromatolitic builders as both modern and Precambrian stromatolite-forming microorganisms; (2) Based on the fact that the chain fossils are preserved perpendicularly to the laminations the rates of sedimentation and algal growth were probably equal and each small sedimentary rhythm could be completed in about one or two months; (3) According to the environment and habits of living Nostoc Precambrian hydrosphere might be of a fresh water type.     

Role of the cyclosporin-A-cyclophilin complex, FK506-FK506-binding protein complex and calcineurin in the inhibition of T-cell signal transduction: Current opinion in structural biology 1993, 3:929–933

SH2 and SH3 domains are small protein modules of about 100 and 60 amino acids, respectively, that are found in many proteins involved in intracellular signal transduction. SH2 and SH3 domains mediate protein-protein interactions and modulate enzyme activity by their ability to bind to specific phosphorylated tyrosine residues or proline-rich sequences, respectively. The recent determination of the three-dimensional structures of several SH2 and SH3 domains has led to considerable progress in understanding their mechanism of action, and these structures are the focus of this review.     

Flexibility of interdomain contacts revealed by topological isomers of bivalent consolidated ligands to the dual Src homology domain SH(32) of abelson

Src homology (SH)2 and SH3 domains are found in a variety of proteins involved in the control of cellular signaling and architecture. The possible interrelationships between domains are not easily investigated, even though several cases of multiple domain-containing constructs have been studied structurally. As a complement to direct structural methods, we have developed consolidated ligands and tested their binding to the Abl SH(32) complex. Consolidated ligands combine in the same molecule peptide sequences recognized by SH2 and SH3 domains, i.e., Pro-Val-pTyr-Glu-Asn-Val and Pro-Pro-Ala-Tyr-Pro-Pro-Pro-Pro-Val-Pro, respectively; these are joined by oligoglycyl linkers. Four types of ligands were chemically synthesized, representing all the possible relative orientations of ligands. Their affinities were found to vary with binding portion topologies and linker lengths. Two of these types were shown to bind to both SH2 and SH3 dual domains with high affinities and specificities, showing increases of one order of magnitude, as compared to the most strongly bound monovalent equivalent. These results suggest that the relative orientation of SH2 and SH3 in Abl SH(32) is not fixed, and this synthetic approach may be generally useful for determining the structures of ligated complexes and for developing reagents with high affinities and specificities.     

Crystal Structure of the Src Family Kinase Hck SH3-SH2 Linker Regulatory Region Supports an SH3-dominant Activation Mechanism

Most mammalian cell types depend on multiple Src family kinases (SFKs) to regulate diverse signaling pathways. Strict control of SFK activity is essential for normal cellular function, and loss of kinase regulation contributes to several forms of cancer and other diseases. Previous x-ray crystal structures of the SFKs c-Src and Hck revealed that intramolecular association of their Src homology (SH) 3 domains and SH2 kinase linker regions has a key role in down-regulation of kinase activity. However, the amino acid sequence of the Hck linker represents a suboptimal ligand for the isolated SH3 domain, suggesting that it may form the polyproline type II helical conformation required for SH3 docking only in the context of the intact structure. To test this hypothesis directly, we determined the crystal structure of a truncated Hck protein consisting of the SH2 and SH3 domains plus the linker. Despite the absence of the kinase domain, the structures and relative orientations of the SH2 and SH3 domains in this shorter protein were very similar to those observed in near full-length, down-regulated Hck. However, the SH2 kinase linker adopted a modified topology and failed to engage the SH3 domain. This new structure supports the idea that these noncatalytic regions work together as a “conformational switch” that modulates kinase activity in a manner unique to the SH3 domain and linker topologies present in the intact Hck protein. Our results also provide fresh structural insight into the facile induction of Hck activity by HIV-1 Nef and other Hck SH3 domain binding proteins and implicate the existence of innate conformational states unique to individual Src family members that “fine-tune” their sensitivities to activation by SH3-based ligands.     

Crystal structure of Src-like adaptor protein 2 reveals close association of SH3 and SH2 domains through β-sheet formation

The Src-like adaptor proteins (SLAP/SLAP2) are key components of Cbl-dependent downregulation of antigen receptor, cytokine receptor, and receptor tyrosine kinase signaling in hematopoietic cells. SLAP and SLAP2 consist of adjacent SH3 and SH2 domains that are most similar in sequence to Src family kinases (SFKs). Notably, the SH3–SH2 connector sequence is significantly shorter in SLAP/SLAP2 than in SFKs. To understand the structural implication of a short SH3–SH2 connector sequence, we solved the crystal structure of a protein encompassing the SH3 domain, SH3–SH2 connector, and SH2 domain of SLAP2 (SLAP2–32). While both domains adopt typical folds, the short SH3–SH2 connector places them in close association. Strand βe of the SH3 domain interacts with strand βA of the SH2 domain, resulting in the formation of a continuous β sheet that spans the length of the protein. Disruption of the SH3/SH2 interface through mutagenesis decreases SLAP-32 stability in vitro, consistent with inter-domain binding being an important component of SLAP2 structure and function. The canonical peptide binding pockets of the SH3 and SH2 domains are fully accessible, in contrast to other protein structures that display direct interaction between SH3 and SH2 domains, in which either peptide binding surface is obstructed by the interaction. Our results reveal potential sites of novel interaction for SH3 and SH2 domains, and illustrate the adaptability of SH2 and SH3 domains in mediating interactions. As well, our results suggest that the SH3 and SH2 domains of SLAP2 function interdependently, with implications on their mode of substrate binding.     

Carbon isotopic composition of Frutexites in subseafloor ultramafic rocks

Micrometer sized stromatolitic structures called Frutexites are features observed in samples from the deep subsurface, and hot-spring environments. These structures are comprised of fine laminations, columnar morphology, and commonly consist of iron oxides, manganese oxides, and/or carbonates. Although a biological origin is commonly invoked, few reports have shown direct evidence of their association with microbial activity. Here, we report for the first time the occurrence of subsurface manganese-dominated Frutexites preserved within carbonate veins in ultramafic rocks. To determine the biogenicity of these putative biosignatures, we analyzed their chemical and isotopic composition using Raman spectroscopy and secondary ion mass spectroscopy (SIMS). These structures were found to contain macromolecular carbon signal and have a depleted ¹³C/¹²C carbon isotopic composition of – 35.4?±?0.50‰ relative to the entombing carbonate matrix. These observations are consistent with a biological origin for the observed Frutexites structures.

     

The impact of either 4-R-hydroxyproline or 4-R-fluoroproline on the conformation and SH3m-cort binding of HPK1 proline-rich peptide

SH3 domains are probably the most abundant molecular-recognition modules of the proteome. A common feature of these domains is their interaction with ligand proteins containing Pro-rich sequences. Crystal and NMR structures of SH3 domains complexes with Pro-rich peptides show that the peptide ligands are bound over a range of up to seven residues in a PPII helix conformation. Short proline-rich peptides usually adopt little or no ordered secondary structure before binding interactions, and consequently their association with the SH3 domain is characterized by unfavorable binding entropy due to a loss of rotational freedom on forming the PPII helix. With the aim to stabilize the PPII helix conformation into the proline-rich decapeptide PPPLPPKPKF (P2), we replaced some proline residues either with the 4(R)-4-fluoro-l-proline (FPro) or the 4(R)-4-hydroxy-l-proline (Hyp). The interactions of P2 analogues with the SH3 domain of cortactin (SH3_m-cort) were analyzed by circular dichroism spectroscopy, while CD thermal transition experiments have been used to determine their propensity to adopt a PPII helix conformation. Results show that the introduction of three residues of Hyp efficiently stabilizes the PPII helix conformation, while it does not improve the affinity towards the SH3 domain, suggesting that additional forces, e.g., electrostatic interactions, are involved in the SH3_m-cort substrate recognition.     

The last toothed Productellinae in Europe

The known Productellinae from the Pilton Beds in N. Devon, England and from the Angertal Beds and Étroeungt Beds in the Bergisches Land, Germany are revised. The two subgeneraProductella (Whidbornella) andP. (Hamlingella) are redefined and a new subgenus,P. (Steinhagella), is proposed.P. (Whidbornella) andP. (Hamlingella) seem to be restricted to a sandstone-shale, Pilton-type facies, and both, together withP. (Steinhagella) become extinct in Europe at the top of the Devonian.     

Primary structure and functional characterization of rat C5a: an anaphylatoxin with unusually high potency.

The anaphylatoxin C5a is a pro-inflammatory factor generated from C5 during complement activation. C5a derived from rat C5 exhibits significantly greater potency compared to C5a from other species. Rat C5a was 25-fold more potent than human C5a for eliciting spasmogenic contraction of guinea pig ileum. Proteolytic removal of the C-terminal arginine of C5a (C5adesArg) reduced spasmogenic potency of rat C5a by only 4-fold compared to a 3,000-fold reduction for human C5adesArg. In addition, rat C5adesArg was 50-fold more potent than human C5adesArg in a guinea pig vascular permeability (in vivo) assay and as a chemotactic factor for human neutrophils. C5a and C5adesArg were purified from zymosan-activated rat serum. Rat C5a, like human C5a, is glycosylated but contains 77 amino acid residues instead of the 74 residues of human C5a. Comparison of the primary structures of rat and human C5a indicated differences at 30 positions including an insert of 3 residues (LLH) in the rat molecule between residue positions 3 and 4 in human C5a. Insertion of residues LLH between Gln-3 and Lys-4 in a recombinant human C5a molecule using site-directed mutagenesis failed to enhance potency. Synthetic C-terminal analogues of rat C5a proved to be measurably more potent than the corresponding human C5a analogues (Ember JA et al., 1993, Protein Sci 2(Suppl 1):159 [Abstr]). We conclude that multiple sequence differences in the C-terminal effector portion and/or elsewhere in rat C5a, but not the LLH insert, account for the significant enhancement in potency of rat C5a over C5a from other species.     

Stiffness of the distal loop restricts the structural heterogeneity of the transition state ensemble in SH3 domains

Protein engineering experiments and Phi(F)-value analysis of SH3 domains reveal that their transition state ensemble (TSE) is conformationally restricted, i.e. the fluctuations in the transition state (TS) structures are small. In the TS of src SH3 and alpha-spectrin SH3 the distal loop and the associated hairpin are fully structured, while the rest of the protein is relatively disordered. If native structure predominantly determines the folding mechanism, the findings for SH3 folds raise the question: What are the features of the native topology that determine the nature of the TSE? We propose that the presence of stiff loops in the native state that connect local structural elements (such as the distal hairpin in SH3 domains) conformationally restricts TSE. We validate this hypothesis using the simulations of a "control" system (16 residue beta-hairpin forming C-terminal fragment of the GBl protein) and its variants. In these fragments the role of bending rigidity in determining the nature of the TSE can be directly examined without complications arising from interactions with the rest of the protein. The TSE structures in the beta-hairpins are determined computationally using cluster analysis and limited Phi(F)-value analysis. Both techniques prove that the conformational heterogeneity decreases as the bending rigidity of the loop increases. To extend this finding to SH3 domains a measure of bending rigidity based on loop curvature, which utilizes native structures in the Protein Data Bank (PDB), is introduced. Using this measure we show that, with few exceptions, the ordering of stiffness of the distal, n-src, and RT loops in the 29 PDB structures of SH3 domains is conserved. Combining the simulation results for beta-hairpins and the analysis of PDB structures for SH3 domains, we propose that the stiff distal loop restricts the conformational fluctuations in the TSE. We also predict that constraining the distal loop to be preformed in the denatured ensemble should not alter the nature of TSE. On the other hand, if the amino and carboxy terminals are cross-linked to form a circular polypeptide chain, the pathways and TSs are altered. These contrasting scenarios are illustrated using simulations of cross-linked WT beta-hairpin fragments. Computations of bending rigidities for immunoglobulin-like domain proteins reveal no clear separation in the stiffness of their loops. In the beta-sandwich proteins, which have large fractions of non-local native contacts, the nature of the TSE cannot be apparently determined using purely local structural characteristics. Nevertheless, the measure of loop stiffness still provides qualitative predictions of the ordered regions in the TSE of Ig27 and TenFn3.     

The Hunneberg Stage (Ordovician) in the area east of St. Petersburg, north-western Russia

The bio- and lithostratigraphy of the poorly known early Ordovician (Arenig) Hunneberg Stage is described from the area east of St. Petersburg (Putilovo Quarry and Lava river), where the Lakity Beds (Leetse Fm.) consist of glauconitic sands and silty clays. The described fauna includes graptolites, conodonts, brachiopods, acritarchs, foraminifers, and several problematic groups. The Lakity Beds are unique within the lower Ordovician sequence of the East Baltic in the abundance of graptolites, co-occurring with conodonts. The conodonts from the lower part of the Lakity Beds belong to the uppermost subzone (Oelandodus elongatus — Acodus deltatus deltatus) of theParoistodus proteus Zone, coinciding with the lower part of theTetragraptus phyllograptoides Zone. This suggests that there is a hiatus between the Lakity Beds and the underlying Nazya Formation. The lower Lakity Beds also contain the brachiopodsLeptembolon lingulaeformis andEosiphonotreta cf.acrotretomorpha, which suggest that they may be correlated with the Joa Member of the Leetse Formation in North Estonia. In the upper part of the Lakity Beds, conodonts of thePrioniodus elegans Zone co-occur with graptolites indicating the upper subzone of theTetragraptus phyllograptoides Zone in the Scandinavian sections. There are still problems of defining and correlating the base of the Billingen Regional Stage, which are outside the scope of this paper.     

Effect of silkworm hemolymph on N-linked glycosylation in two Trichoplusia ni insect cell lines

A recombinant N-linked glycoprotein, secreted human placental alkaline phosphatase (SEAP), was produced in two Trichoplusia ni insect cell lines using the baculovirus expression vector. Silkworm hemolymph (SH) was added to TNMFH + 10% fetal bovine serum (FBS) medium to a concentration of 2.5% or 5%, and SEAP production and glycosylation in the presence of SH were compared with controls devoid of hemolymph. Growing Tn-4s cells in 5% SH-supplemented medium required progressive adaptation of the cells to SH, and adapted cells had a SEAP specific yield decreased by 2.5-fold compared with control cells not exposed to SH. Although SEAP produced in the control possessed little complex glycosylation (<1%), SEAP produced by SH-adapted cells in the presence of 5% SH possessed 8.7% sialylated structures, as well as unusual, asialylated, agalactosylated structures with a high degree of polymerization (DP). On the basis of enzymatic and mass-spectrometric analyses, we propose that these structures are glucosylated, high-mannose oligosaccharides. SEAP was also produced by Tn-4s cells without adaptation to SH when SH was added just prior to baculovirus infection, but SEAP specific yield was adversely affected (approximately fourfold reduction compared with control devoid of hemolymph), and glycosylation of SEAP produced under these conditions was characterized by large amounts of high-mannose and high-DP structures and an absence of complex structures. Similarly, Tn5B1-4 cells that were not adapted to SH had a SEAP specific yield reduced by approximately fivefold in SH-containing medium; however, these cells were able to produce 13.5% sialylated SEAP in the presence of 2.5% SH, whereas complex structures were not produced in the absence of SH. We propose that SH improves glycosylation either directly or indirectly by decreasing SEAP specific yield.     

P120-Ras GTPase activating protein (RasGAP): A multi-interacting protein in downstream signaling

p120-RasGAP (Ras GTPase activating protein) plays a key role in the regulation of Ras-GTP bound by promoting GTP hydrolysis via its C-terminal catalytic domain. The p120-RasGAP N-terminal part contains two SH2, SH3, PH (pleckstrin homology) and CaLB/C2 (calcium-dependent phospholipid-binding domain) domains. These protein domains allow various functions, such as anti-/pro-apoptosis, proliferation and also cell migration depending of their distinct partners. The p120-RasGAP domain participates in protein–protein interactions with Akt, Aurora or RhoGAP to regulate functions described bellow. Here, we summarize, in angiogenesis and cancer, the various functional roles played by p120-RasGAP domains and their effector partners in downstream signaling.