IGF-I receptor phosphorylation is impaired in cathepsin X-deficient prostate cancer cells

The cysteine-type peptidase cathepsin X is highly upregulated in several cancers and presumably promotes tumor invasion through bypassing cellular senescence. Here, we present first evidence that the underlying mechanism may involve the regulation of the insulin-like growth factor (IGF) system, a well-known activator of proliferating tumor cells. Cathepsin X deficiency leads to a reduced phosphorylation of the IGF-I receptor in response to IGF-I stimulation. In addition, downstream signaling through focal adhesion kinase was also affected. Taken together, our results indicate that cathepsin X is able to assist in IGF signaling, which may be an important progress toward understanding cathepsin X-dependent tumorigenesis

Temporary inhibition of papain by hairpin loop mutants of chicken cystatin Distorted binding of the loops results in cleavage of the Gly9-Ala10 bond

AbstractTemporary inhibition of the cysteine proteinases papain and cathepsin L was observed with several hairpin loop mutants of recombinant chicken cystatin at enzyme concentrations above nanomolar. Kinetic modelling of inhibition data, gel electrophoresis and amino acid sequencing revealed that reappearance of papain activity is due to selective cleavage of the Gly9-Ala10 bond in the N-terminal binding area of the chicken cystatin variants, resulting in truncated inhibitors of lower affinity. Cleavage of the same bond by contaminating papaya proteinase IV was ruled out by previous purification of papain and suitable control experiments. According to the proposed kinetic model, cleavage occurs within the enzyme-inhibitor complex with first order rate constants ktemp of 2.3 × 10−3 up to 5 × 10−1 s−1. A similar ktempKm ratio was found for all mutants (0.7 × 106–2.1 × 106 s−1·M−1); it is almost identical with the kcatKm ratio of the peptide substrate Z-Phe-Arg-NHMec. These results suggest that distorted contacts of one of the hairpin loops affect binding of the N-terminal contact area in a way that covalent interaction of the Gly9-Ala10 bond with the active-site Cys residue of papain can occur and the bond is cleaved in a substrate-like manner

Data from: Self-recognition in crickets via on-line processing

Self-referent phenotype matching, the ability of animals to use aspects of their own phenotype as a referent in discrimination decisions, is believed to play a significant role in nepotistic interactions and mate choice in a wide range of taxa [1]. An individual’s ability to assess the similarity between its own phenotype and that of the individuals it encounters can provide a reliable measure of relatedness, thereby facilitating inbreeding avoidance, optimal outbreeding or altruistic behavior towards kin 2 and 3. Although self-referencing is believed to be widespread, definitive evidence is scarce and its role in recognition controversial, in part, because of the difficulty in ruling out early exposure to close kin and the possibility that individuals imprint on maternal cues early in their ontogeny, either during birth or via cues encountered upon hatching from eggs 1 and 4. An equally important, yet unanswered question is whether individuals that perform self-referencing imprint on their own traits at an early stage, relying on this memorized template in subsequent interactions, or whether no memory is formed but individuals use their own phenotype directly in comparison with other individuals (i.e., ‘on-line processing’) [3]. Finally, animals may possess ‘recognition alleles’, in which both the phenotypic cues and the knowledge of the cues have a genetic basis [5]. Here we show in the decorated cricket, Gryllodes sigillatus, that female mate choice can be manipulated by experimentally altering a female’s own olfactory cues. We found exclusive evidence both for the existence of a chemosensory self-referencing mechanism and that females do not rely on an innate or early learned template but rather directly use their own phenotypic cues in comparison

Data from: Self-recognition in crickets via on-line processing

Self-referent phenotype matching, the ability of animals to use aspects of their own phenotype as a referent in discrimination decisions, is believed to play a significant role in nepotistic interactions and mate choice in a wide range of taxa [1]. An individual’s ability to assess the similarity between its own phenotype and that of the individuals it encounters can provide a reliable measure of relatedness, thereby facilitating inbreeding avoidance, optimal outbreeding or altruistic behavior towards kin 2 and 3. Although self-referencing is believed to be widespread, definitive evidence is scarce and its role in recognition controversial, in part, because of the difficulty in ruling out early exposure to close kin and the possibility that individuals imprint on maternal cues early in their ontogeny, either during birth or via cues encountered upon hatching from eggs 1 and 4. An equally important, yet unanswered question is whether individuals that perform self-referencing imprint on their own traits at an early stage, relying on this memorized template in subsequent interactions, or whether no memory is formed but individuals use their own phenotype directly in comparison with other individuals (i.e., ‘on-line processing’) [3]. Finally, animals may possess ‘recognition alleles’, in which both the phenotypic cues and the knowledge of the cues have a genetic basis [5]. Here we show in the decorated cricket, Gryllodes sigillatus, that female mate choice can be manipulated by experimentally altering a female’s own olfactory cues. We found exclusive evidence both for the existence of a chemosensory self-referencing mechanism and that females do not rely on an innate or early learned template but rather directly use their own phenotypic cues in comparison

Data from: Species divergence in offspring begging and parental provisioning is linked to nutritional dependency

In animal species in which parents provide food to their dependent young, offspring often display conspicuous begging signals. These solicitation behaviors are important components of parent–offspring communication, but it is currently unclear how they and the parental response covary with offspring dependency on parental food provisioning across species. Burying beetles (Nicrophorus) are well known for providing elaborate biparental care, including provisioning of begging larvae. By using a multispecies approach, we show that larval begging intensity, as well as the time parents spend provisioning, differ greatly between individuals of the 3 species: N. orbicollis, N. pustulatus, and N. vespilloides. Our results demonstrate that the most dependent offspring of N. orbicollis invest the most time in begging, whereas the most independent offspring of N. pustulatus invest the least amount of time in begging. Thus, we suggest that begging intensity differs due to intrinsic differences in nutritional need between the species rather than because of an arbitrary divergence in begging behavior. We further show that in all 3 species, females spend significantly more time provisioning than males, although there is considerable divergence between species in the extent to which females and males contribute to the provisioning of larvae. We discuss the potential selective factors leading to this diversification of offspring begging and parental provisioning in relation to the distinct variation in offspring dependence between the 3 species