Ralph Bradshaw

Ralph Bradshaw
University of California, Irvine | UCI · Department of Physiology & Biophysics

Ph.D.

About

418
Publications
13,545
Reads
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19,063
Citations
Citations since 2016
25 Research Items
2073 Citations
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2016201720182019202020212022050100150200250300
2016201720182019202020212022050100150200250300
Additional affiliations
October 2006 - June 2015
University of California, San Francisco
Position
  • Professor

Publications

Publications (418)
Chapter
Cell communication is the driving force that enables the development and functioning of all multicellular organisms. From reproduction and embryogenesis to cellular and tissular homeostasis in the adult, the control of metabolism and general physiology, as well as the dysregulations in pathological processes, cell communication is germane to all as...
Chapter
Plasma and tissue kallikreins were defined by their ability to liberate the vasoactive peptides, kinins, from kininogens. Plasma kallikrein functions in the vascular space and is responsible for the formation of bradykinin. It also participates in the contact phase of blood coagulation. Tissue kallikrein is present in glandular secretions and in th...
Chapter
The determination of the first protein sequence (insulin) was a landmark achievement that confirmed proteins were composed of a specific order of amino acid residues and lead to the development of methods, many eventually automated, for the rapid sequence analysis of a wide variety of proteins. Much of this technology was devoted to the isolation o...
Article
Full-text available
Utilising rabbit corneal endothelial cells (CEC) in three different paradigms, two human FGF1 derivatives (TTHX1001 and TTHX1114), engineered to exhibit greater stability, were tested as proliferative agents. Primary CECs and mouse NIH 3T3 cells treated with the two FGF1 derivatives showed equivalent EC50 ranges (3.3–24 vs.1.9–16. ng/mL) and, in or...
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Purpose: Caveolin (Cav) regulates various aspect of endothelial cell signaling and cell-permeable peptides (CPPs) fused to domains of Cav can reduce retinal damage and inflammation in vivo. Thus, the goal of the present study was to identify a novel CPP that improves delivery of a truncated Cav modulator in vitro and in vivo. Methods: Phage disp...
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Although the long‐awaited arrival of 2021 has come and gone, it has already become symbolic of new (and generally very much better) times. Although it is undoubtedly going to share some of the COVID‐19 misery/disruption with its predecessor, it also promises to be the year we see it dismissed. Sadly, picking up the pieces will extend far beyond it.
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Dr. Herbert Tabor, biochemist, renowned authority on the synthesis and function of polyamines, and Chief Editor extraordinaire for the Journal of Biological Chemistry (JBC) for approximately 50 years, died August 20th at his home on the National Institutes Health campus in Bethesda Maryland. He was preceded in death by his wife Celia Tabor, a physi...
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In the mid‐1960s, Washington University, located in St. Louis, MO, was a small liberal arts school catering mainly to local students that coincidentally had a large, and highly recognized medical school, populated with some of the best physicians and scientists in the world that disproportionally reflected the prestige of the institution. However,...
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A few months ago, FASEB BioAdvances launched its first special collection that was designed to provide an update on medical school curriculum discussions and examine the impact of the pandemic on them1. Of course, COVID 19 has disrupted all teaching activities at every level from kindergarten to professional schools, along with about every other as...
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A few months ago, we announced that FASEB BioAdvances would be extending its coverage beyond just articles in biomedicine and biology to include reports on history, science policy and society and biomedical education.
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Purpose: Corneal endothelial dystrophies are characterized by endothelial cell loss and dysfunction. Recent evidence suggests that corneal endothelial cells (CECs) can regenerate although they do not do so under normal conditions. This work sought to test whether CECs can be stimulated to proliferate in organ culture by wounding and/or by treatment...
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We are now over three months into a viral pandemic (COVID 19) that has already left a trail of death and destruction, wreaking social and economic havoc, and disrupting, in most parts of the world, just about every aspect of life—and it is far from over. It is therefore a source of some pride that the scientific and medical professions have respond...
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The Federation of American Societies for Experimental Biology (FASEB) was formed in 1912 to serve the needs of its four charter societies. Its growth, from these organizations with a little more than 300 members to nearly 30 societies with over 100,000 members, is a tribute to its ability to respond to the changing structure and needs of the experi...
Article
Despite progress in genomic and proteomic technology and applications, the validation of cancer biomarkers of use as clinical early detection diagnostics has remained elusive. As described in this brief viewpoint, there are now recognized to be many types of clinical biomarkers and proteomic analyses, particularly when combined with other 'omic ana...
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Purpose Organ cultures of rabbit corneas have been used to ascertain the effectiveness of a human fibroblast growth factor (FGF)-1 derivative (TTHX1114), lacking cysteine residues, to protect against and/or repair epithelial lesions following exposure to nitrogen mustard (NM). Methods Rabbit corneas were exposed to NM and cultured for up to 14 day...
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Nerve growth factor (NGF) is a protein whose importance to research and its elucidation of fundamental mechanisms in cell and neurobiology far outstrips its basic physiological roles. It was the first of a broad class of cell regulators, largely acting through autocrine and paracrine interactions which will be described herein. It was of similar si...
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Full-text available
Molecular & Cellular Proteomics is pleased to announce new guidelines and requirements for papers describing the development and application of targeted mass spectrometry measurements of peptides, modified peptides and proteins. These guidelines will be implemented for papers submitted starting June, 2017.
Article
Plasma and tissue kallikreins were initially defined by their ability to liberate vasoactive peptides, kinins, from kininogens. Plasma kallikrein functions in the vascular space and is responsible for the formation of bradykinin. It also participates in the contact phase of blood coagulation. Tissue kallikrein occurs in glandular secretions and in...
Article
The determination of the first protein sequence (insulin) was a landmark achievement that confirmed proteins were composed of a specific order of amino acid residues and lead to the development of methods, many eventually automated, for the rapid sequence analysis of a wide variety of proteins. Much of this technology was devoted to the isolation o...
Article
Full-text available
The Centre for Cellular and Molecular Biology, Hyderabad, India was host for an international forum or brainstorming meeting on proteomics held in November, 2014, which provided the opportunity to showcase proteomic science in India and to allow discussions between Indian scientists and students and several international visitors. This provided an...
Chapter
Protein phosphorylation represents one of the most prevalent posttranslational modifications (PTMs) in mammalian cellular processes and is most easily identified/measured by mass spectrometry or with specific recognition molecules, such as antibodies, usually in an array format. Phosphorylation of the phenolic group of tyrosine occurs to a much les...
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Full-text available
Brain metastases are a devastating consequence of cancer and currently there are no specific biomarkers or therapeutic targets for risk prediction, diagnosis, and treatment. Here the proteome of the brain metastatic breast cancer cell line 231-BR has been compared with that of the parental cell line MDA-MB-231, which is also metastatic but has no o...
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Infiltration of the tumor microenvironment by nerve fibers is an understudied aspect of breast carcinogenesis. In this study, the presence of nerve fibers was investigated in a cohort of 369 primary breast cancers (ductal carcinomas in situ, invasive ductal and lobular carcinomas) by immunohistochemistry for the neuronal marker PGP9.5. Isolated ner...
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The journal is pleased to announce that it is launching an upgraded mini-review program to enhance its coverage of topics of timely interest to the proteomics community and beyond. Copyright © 2015, The American Society for Biochemistry and Molecular Biology.
Article
The Trk family is composed of three principal members (A, B and C), also termed neurotrophin tyrosine kinase receptors (NTRK1, NTRK2, NTRK3), with several additional splice variants, which in humans are located on three different chromosomes (1, 9, 15). The Trk proteins are receptors for the neurotrophin family of growth factors (NGF, BDNF, NT-3, a...
Article
Nerve infiltration is essential to prostate cancer progression, but the mechanism by which nerves are attracted to prostate tumors remains unknown. We report that the precursor of nerve growth factor (proNGF) is overexpressed in prostate cancer and involved in the ability of prostate cancer cells to induce axonogenesis. A series of 120 prostate can...
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Adoption of targeted mass spectrometry (MS) approaches such as multiple reaction monitoring (MRM) to study biological and biomedical questions is well underway in the proteomics community. Successful application depends on the ability to generate reliable assays that uniquely and confidently identify target peptides in a sample. Unfortunately, ther...
Chapter
This chapter elaborates the activity, specificity and structural chemistry of methionyl aminopeptidase type 1 (MetAP 1). Two classes of aminopeptidases have been isolated that are involved in the nonprocessive cleavage of the methionine + residue that initiates protein synthesis. Both classes of MetAPs have the same general specificity based on the...
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Receptor tyrosine kinases generally act by forming phosphotyrosine-docking sites on their own endodomains that propagate signals through cascades of post-translational modifications driven by the binding of adaptor/effector proteins. The pathways that are stimulated in any given receptor tyrosine kinase are a function of the initial docking sites t...
Chapter
Aminopeptidases, which are widely distributed in nature, are one of the two major subclasses of the exopeptidases, proteolytic enzymes that remove amino acids from the termini of peptides and proteins (the other being the carboxypeptidases). As the name indicates, the aminopeptidases attack their substrates exclusively from the amino terminal end....
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N-terminal methionine excision (NME) and N-terminal acetylation (NTA) are two of the most common protein post-translational modifications. NME is a universally conserved activity and a highly specific mechanism across all life forms. NTA is very common in eukaryotes but occurs rarely in prokaryotes. By analyzing data sets from yeast, mammals and ba...
Article
Receptor tyrosine kinases (RTKs) function through protein kinase entities located in the intracellular domain of each protomer. Following activation by ligand binding, they selectively form phosphotyrosine residues by autocatalytic modification. Some of these sites are involved in maintaining the active conformation of the kinase, while others beco...
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Policies supporting the rapid and open sharing of proteomic data are being implemented by the leading journals in the field. The proteomics community is taking steps to ensure that data are made publicly accessible and are of high quality, a challenging task that requires the development and deployment of methods for measuring and documenting data...
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The precursor of nerve growth factor (proNGF) has been described as a biologically active polypeptide able to induce apoptosis in neuronal cells, via the neurotrophin receptor p75(NTR) and the sortilin receptor. Herein, it is shown that proNGF is produced and secreted by breast cancer cells, stimulating their invasion. Using Western blotting and ma...
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Stably transfected PC12 cells expressing a chimeric receptor composed of the extracellular domain of the platelet-derived growth factor receptor BB and the transmembrane and intracellular domains of TrkA, the nerve growth factor receptor, were stimulated for 20 min with platelet-derived growth factor and the resulting phosphoproteome was determined...
Article
Given the essential role of proteomics in understanding the biology of plants, we are establishing a global plant proteomics organization to properly organize, preserve and disseminate collected information on plant proteomics. We call this organization 'International Plant Proteomics Organization (INPPO; http://www.inppo.com).' Ten initiatives of...
Chapter
The central importance of the general phenomenon of sensing of external stimuli by cells has been appreciated for a long time, but has truly become a dominant part of cell and molecular biology research in the past two decades, in part because a description of the dynamic responses of cells to external stimuli is in essence a description of the lif...
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The RTKs are one of the most important families mediating transmembrane signaling and they participate and are instrumental in regulating a broad range of physiological activities. Indeed, tyrosine kinases in general, and the processes that they control and/or stimulate, provide a rich source of drug targets, particularly in growth related disorder...
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Analysis of protein post-translational modifications using mass spectrometry is an intensive area of proteomic research. This perspective discusses the current state of the field with respect to what can be achieved, the challenges encountered, most notably with modification site assignment, the reliability of the published results, consequences of...
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As the journal moves into its tenth year of publication, it (really those charged with its editorial well-being) continues to monitor developments in the field of proteomics, including activities in the related fields of genomics, transcriptomics and metabolomics, with the view of introducing appropriate changes to accommodate them. This includes k...
Book
KEY FEATURES: * Contains over 350 chapters of comprehensive coverage on cell signaling * Includes discussion on topics from ligand/receptor interactions to organ/organism responses * Provides user-friendly, well-illustrated, reputable content by experts in the field DESCRIPTION: Handbook of Cell Signaling, Three-Volume Set, 2e, is a comprehensive w...
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Co-editors With this issue, we initiate a new phase of the association of MCP with the Human Proteome Organisation (HUPO), a rela-tionship that extends back to the inception of both ventures. Since the now historic first congress in Versailles in November 2002, MCP has been privileged to publish the abstracts/ program of every HUPO congress. This w...
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Nerve growth factor (NGF) is the ligand for two unrelated cellular receptors, TrkA and p75NTR, and acts as a mediator in the development and maintenance of the mammalian nervous system. Signaling through TrkA kinase domains promotes neuronal survival, whereas activation of the p75NTR “death domains” induces apoptosis under correct physiological con...
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Mutations in fibroblast growth factor receptor 3 (FGFR3) cause the most common genetic form of short-limbed dwarfism, achondroplasia (ACH), as well as neonatal lethal forms, thanatophoric dysplasia (TD) I and II. The causative mutations induce graded levels of constitutive activation of the receptor that correspond to the severity of the disorder,...
Article
During the second half of the 20th century, biochemistry and subsequently molecular biology blossomed into the core upon which all biological and biomedical sciences now depend. A major part of these closely related disciplines has been the study of the structure and function of proteins and the diverse biological functions that they perform. Early...
Article
Methionine, used to initiate protein synthesis in eukaryotes, is largely recovered as a co-translational hydrolysis event catalysed by two related enzymes, methionine aminopeptidase (MetAP)1 and 2. One of these, MetAP2, is covalently modified, and thus catalytically inactivated, by a class of drugs related to the fungal polyene antibiotic, fumagill...
Article
To assess whether nerve growth factor (NGF) expression would respond to booster dosing with the inducing agent ponasterone A, human embryonic kidney cells (HEK-293) were transfected with human NGF cDNA. Cells were cultured for 5 days in media with or without ponasterone A. On day 5, controls received a ponasterone A media replacement, whereas exper...
Article
Tissue-engineering strategies offer hope to patients facing functional impairment after nerve injury. We have previously demonstrated that HEK-293 cells can release nerve growth factor (NGF) in vitro, using an inducible system of expression. In this study, our objective was to assess the efficacy of the NGF delivery system in vivo, using nude rats....
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Thrombin is the product of the hemostatic response essential to the conversion of fibrinogen to fibrin. In addition, it is also responsible for the aggregation of blood platelets in the formation of the "platelet plug" as well as the activation of factor VIII, factor V, factor XI, factor XIII and protein C. The action of thrombin is not confined to...
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Protein sulfonation on serine and threonine residues is described for the first time. This post-translational modification is shown to occur in proteins isolated from organisms representing a broad span of eukaryote evolution, including the invertebrate mollusk Lymnaea stagnalis, the unicellular malaria parasite Plasmodium falciparum, and humans. D...
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The development of engineered constructs to bridge nerve gaps may hold the key to improved functional outcomes in the repair of injured peripheral nerves. These constructs must be rendered bioactive by providing the growth factors required for successful peripheral nerve regeneration. Previous studies demonstrated that harvested human and rat derma...
Chapter
This chapter provides a brief description on how oligomerization is utilized by the major cell transmembrane receptor classes. The cell-surface receptors possessing intrinsic tyrosine kinase activity (RTK) minimally require a dimeric state for their full activity. RTK dimerization occurs as a result of ligand binding, and the ligand-bound monomer t...
Chapter
This chapter gives an overview on cell-cell and cell-matrix interactions. Cell signaling pathways form extensive interactive networks that results in the distinctive features distinguishing many of the response properties of specific tissues and organs. An idea that chemical signals may be provided locally or regionally in tissues by a group of mec...
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Full-text available
A long-standing question in neurotrophin signal transduction is whether heteromeric TrkA-p75NTR complexes possess signaling capabilities that are significantly different from homo-oligomeric TrkA or p75NTR alone. To address this issue, various combinations of transfected PC12 cells expressing a platelet-derived growth factor receptor-TrkA chimera a...
Article
PC12 cells have been used as a model system for neuronal differentiation due to their ability to alter their phenotype to a sympathetic neuron-like cell in response to nerve growth factor or fibroblast growth factor. Under some conditions, epidermal growth factor (EGF) can also induce PC12 cells to differentiate. To study signaling from the EGF rec...