The Experts below are selected from a list of 34038 Experts worldwide ranked by ideXlab platform
Takashi Miyata - One of the best experts on this subject based on the ideXlab platform.
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motifs of cadherin and fibronectin type iii related sequences and evolution of the receptor type protein tyrosine Kinases sequence similarity between proto oncogene ret and cadherin family
Molecular Biology and Evolution, 1993Co-Authors: Keiichi Kuma, Naoyuki Iwabe, Takashi MiyataAbstract:: Immunoglobulin (Ig)-, fibronectin type III (FN-III)-, and cadherin-related sequences are often found in multiple repeats in the extracellular regions of various cell adhesion molecules. The amino acid sequences of 82 different cadherin-like repeats from 13 known members of the cadherin superfamily were compared for six highly conserved regions, and a frequency matrix represented as amino acids versus position matrix was calculated based on the alignment. With the frequency matrix, further members of the cadherin superfamily were searched for in the protein data base. It was found that the ret protein, a receptor-type-protein tyrosine kinase, contains cadherin-like repeats in the extracellular region. A similar analysis was also carried out for the FN-III superfamily. Nine receptor-type-protein tyrosine Kinases were shown to exhibit significant similarities, in terms of sequence, with known FN-III-like repeats. Several receptor-type-protein tyrosine Kinases have already been reported to have Ig-like repeats in their extracellular regions. Thus these receptor-type-protein tyrosine Kinases--together with the remaining receptors, whose structures are not yet characterized--may be classified into at least four distinct groups based on the structural differences in the extracellular domains. A molecular phylogenetic tree inferred from the shared kinase domains of these receptor-type-protein tyrosine Kinases revealed a close relationship between the branching patterns and the grouping based on the structural differences of the extracellular region.
E Y Jones - One of the best experts on this subject based on the ideXlab platform.
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an extracellular steric seeding mechanism for eph ephrin signaling platform assembly
Nature Structural & Molecular Biology, 2010Co-Authors: E Seiradake, K Harlos, G Sutton, A R Aricescu, E Y JonesAbstract:Eph receptors are cell surface protein tyrosine Kinases that mediate cell-cell communication. The crystal structure of the full ectodomain of unliganded human EphA2 (eEphA2) reveals that it forms linear arrays of staggered, parallel receptors, whereas that of eEphA2 in complex with ephrinA5 forms a more elaborate assembly with interfaces that are crucial for localization at cell-cell contacts and for activation-dependent degradation.
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an extracellular steric seeding mechanism for eph ephrin signaling platform assembly
Nature Structural & Molecular Biology, 2010Co-Authors: E Seiradake, K Harlos, G Sutton, A R Aricescu, E Y JonesAbstract:Eph receptors are cell surface protein tyrosine Kinases that mediate cell-cell communication. The crystal structure of the full ectodomain of unliganded human EphA2 (eEphA2) reveals that it forms linear arrays of staggered, parallel receptors, whereas that of eEphA2 in complex with ephrinA5 forms a more elaborate assembly with interfaces that are crucial for localization at cell-cell contacts and for activation-dependent degradation. Erythropoetin-producing hepatoma (Eph) receptors are cell-surface protein tyrosine Kinases mediating cell-cell communication. Upon activation, they form signaling clusters. We report crystal structures of the full ectodomain of human EphA2 (eEphA2) both alone and in complex with the receptor-binding domain of the ligand ephrinA5 (ephrinA5 RBD). Unliganded eEphA2 forms linear arrays of staggered parallel receptors involving two patches of residues conserved across A-class Ephs. eEphA2–ephrinA5 RBD forms a more elaborate assembly, whose interfaces include the same conserved regions on eEphA2, but rearranged to accommodate ephrinA5 RBD. Cell-surface expression of mutant EphA2s showed that these interfaces are critical for localization at cell-cell contacts and activation-dependent degradation. Our results suggest a 'nucleation' mechanism whereby a limited number of ligand-receptor interactions 'seed' an arrangement of receptors which can propagate into extended signaling arrays.
Gary J. Fisher - One of the best experts on this subject based on the ideXlab platform.
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Receptor type protein tyrosine phosphatases (RPTPs) – roles in signal transduction and human disease
Journal of Cell Communication and Signaling, 2012Co-Authors: Yiru Xu, Gary J. FisherAbstract:Protein tyrosine phosphorylation is a fundamental regulatory mechanism controlling cell proliferation, differentiation, communication, and adhesion. Disruption of this key regulatory mechanism contributes to a variety of human diseases including cancer, diabetes, and auto-immune diseases. Net protein tyrosine phosphorylation is determined by the dynamic balance of the activity of protein tyrosine Kinases (PTKs) and protein tyrosine phosphatases (PTPs). Mammals express many distinct PTKs and PTPs. Both of these families can be sub-divided into non-receptor and receptor subtypes. Receptor protein tyrosine Kinases (RPTKs) comprise a large family of cell surface proteins that initiate intracellular tyrosine phosphorylation-dependent signal transduction in response to binding of extracellular ligands, such as growth factors and cytokines. Receptor-type protein tyrosine phosphatases (RPTPs) are enzymatic and functional counterparts of RPTKs. RPTPs are a family of integral cell surface proteins that possess intracellular PTP activity, and extracellular domains that have sequence homology to cell adhesion molecules. In comparison to extensively studied RPTKs, much less is known about RPTPs, especially regarding their substrate specificities, regulatory mechanisms, biological functions, and their roles in human diseases. Based on the structure of their extracellular domains, the RPTP family can be grouped into eight sub-families. This article will review one representative member from each RPTP sub-family.
Keiichi Kuma - One of the best experts on this subject based on the ideXlab platform.
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motifs of cadherin and fibronectin type iii related sequences and evolution of the receptor type protein tyrosine Kinases sequence similarity between proto oncogene ret and cadherin family
Molecular Biology and Evolution, 1993Co-Authors: Keiichi Kuma, Naoyuki Iwabe, Takashi MiyataAbstract:: Immunoglobulin (Ig)-, fibronectin type III (FN-III)-, and cadherin-related sequences are often found in multiple repeats in the extracellular regions of various cell adhesion molecules. The amino acid sequences of 82 different cadherin-like repeats from 13 known members of the cadherin superfamily were compared for six highly conserved regions, and a frequency matrix represented as amino acids versus position matrix was calculated based on the alignment. With the frequency matrix, further members of the cadherin superfamily were searched for in the protein data base. It was found that the ret protein, a receptor-type-protein tyrosine kinase, contains cadherin-like repeats in the extracellular region. A similar analysis was also carried out for the FN-III superfamily. Nine receptor-type-protein tyrosine Kinases were shown to exhibit significant similarities, in terms of sequence, with known FN-III-like repeats. Several receptor-type-protein tyrosine Kinases have already been reported to have Ig-like repeats in their extracellular regions. Thus these receptor-type-protein tyrosine Kinases--together with the remaining receptors, whose structures are not yet characterized--may be classified into at least four distinct groups based on the structural differences in the extracellular domains. A molecular phylogenetic tree inferred from the shared kinase domains of these receptor-type-protein tyrosine Kinases revealed a close relationship between the branching patterns and the grouping based on the structural differences of the extracellular region.
Takashi Matozaki - One of the best experts on this subject based on the ideXlab platform.
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src family Kinases modulators of neurotransmitter receptor function and behavior
Trends in Neurosciences, 2011Co-Authors: Hiroshi Ohnishi, Yoji Murata, Hideki Okazawa, Takashi MatozakiAbstract:Src family Kinases (SFKs) are non-receptor-type protein tyrosine Kinases that were originally identified as the products of proto-oncogenes and were subsequently implicated in the regulation of cell proliferation and differentiation in the developing mammalian brain. Recent studies using transgenic mouse models have demonstrated that SFKs that are highly expressed in the adult brain regulate neuronal plasticity and behavior through tyrosine phosphorylation of key substrates such as neurotransmitter receptors. Here, we provide an overview of these recent studies, as well as discussing how modulation of the endocytosis of neurotransmitter receptors by SFKs contributes, in part, to this regulation. Deregulation of SFK-dependent tyrosine phosphorylation of such substrates might underlie certain brain disorders.
