RESUMO
Despite the fundamental and practical significance of the hydrogen evolution and oxidation reactions (HER/HOR), their kinetics in base remain unclear. Herein, we show that the alkaline HER/HOR kinetics can be unified by the catalytic roles of the adsorbed hydroxyl (OHad)-water-alkali metal cation (AM+) adducts, on the basis of the observations that enriching the OHad abundance via surface Ni benefits the HER/HOR; increasing the AM+ concentration only promotes the HER, while varying the identity of AM+ affects both HER/HOR. The presence of OHad-(H2O) x-AM+ in the double-layer region facilitates the OHad removal into the bulk, forming OH--(H2O) x-AM+ as per the hard-soft acid-base theory, thereby selectively promoting the HER. It can be detrimental to the HOR as per the bifunctional mechanism, as the AM+ destabilizes the OHad, which is further supported by the CO oxidation results. This new notion may be important for alkaline electrochemistry.
RESUMO
We report the results of a comprehensive study of the relationship between electrochemical performance in Li cells and chemical composition of a series of Li rich layered metal oxides of the general formula xLi2MnO3 · (1-x)LiMn0.33Ni0.33Co0.33O2 in which x = 0,1, 0.2, 0,3, 0.5 or 0.7, synthesized using the same method. In order to identify the cathode material having the optimum Li cell performance we first varied the ratio between Li2MnO3 and LiMO2 segments of the composite oxides while maintaining the same metal ratio residing within their LiMO2 portions. The materials with the overall composition 0.5Li2MnO3 · 0.5LiMO2 containing 0.5 mole of Li2MnO3 per mole of the composite metal oxide were found to be the optimum in terms of electrochemical performance. The electrochemical properties of these materials were further tuned by changing the relative amounts of Mn, Ni and Co in the LiMO2 segment to produce xLi2MnO3 · (1-x)LiMn0.50Ni0.35Co0.15O2 with enhanced capacities and rate capabilities. The rate capability of the lithium rich compound in which x = 0.3 was further increased by preparing electrodes with about 2 weight-percent multiwall carbon nanotube in the electrode. Lithium cells prepared with such electrodes were cycled at the 4C rate with little fade in capacity for over one hundred cycles.
RESUMO
INTRODUCTION: Aspects of social relationships have variably been associated with suicidal ideation (SI) and suicide attempts (SAs). This study assessed whether social support and social distress measures have general factors versus measure-specific factors that are associated with suicide risk. METHODS: Adults (N = 455, 60.0% female), admitted to psychiatric inpatient units following a recent suicide attempt or active SI, completed assessments of social support (emotional support, instrumental support, friendship, perceived support from significant others, friends, family) and social distress (loneliness, perceived rejection, perceived burdensomeness, thwarted belongingness). Bifactor modeling examined general and specific factors of social support and distress in relation to SI (week prior to hospitalization, via the Beck Scale for SI) and SAs (past 30 days, via the Columbia Suicide Severity Rating Scale). RESULTS: SI was significantly associated with the general social support (B = -1.51), the general social distress (B = 1.67), and the specific perceived burdensomeness (B = 1.57) factors. SAs were significantly associated with the specific Perceived Rejection (OR = 1.05) and Thwarted Belongingness (OR = 0.91) factors. CONCLUSION: General social support and social distress were associated with SI but not recent SAs. Specific social distress factors were also related to SI and SAs controlling for general social distress, suggesting areas for future interventions.
RESUMO
Accumulating evidence supports the contention that CD4 and CD8 receptor molecules play a critical signaling role during thymocyte development. The lymphocyte-specific protein tyrosine kinase (p56lck), by virtue of its physical association with these surface components, provides a likely candidate for the biochemical signal transducing element required for these effects. To investigate the function of p56lck in T lymphocytes, transgenic mice were produced that carry either the wild-type lck gene or a mutated lck gene encoding a constitutively activated form of p56lck (p56lckF505). Both transgenes were expressed in thymocytes under the control of the lck proximal promoter element. A large set of founder animals was obtained in which steady-state accumulation of lck transgene mRNA directly correlated with transgene copy number, suggesting that this transgene contains a dominant control region. Progeny of these founders exhibited a transgene-dependent dose-related decrease in the production of thymocytes bearing functional antigen receptors. This effect was strictly dependent on p56lck activity, in that both wild-type and mutated versions of the genes induced similar effects with differing efficiencies. Remarkably, even a twofold increase in p56lck abundance was sufficient to substantially disrupt the appearance of functional thymocytes. These results indicate that thymocyte maturation is regulated in part by signals derived from p56lck.
Assuntos
Proteínas Tirosina Quinases/fisiologia , Linfócitos T/citologia , Timo/citologia , Animais , Antígenos de Diferenciação de Linfócitos T/análise , Complexo CD3 , Antígenos CD4/análise , Antígenos CD8 , Diferenciação Celular , Citometria de Fluxo , Expressão Gênica , Regulação da Expressão Gênica , Vetores Genéticos , Hematopoese , Proteína Tirosina Quinase p56(lck) Linfócito-Específica , Camundongos , Camundongos Transgênicos , Fosfotirosina , Receptores de Antígenos de Linfócitos T/análise , Subpopulações de Linfócitos T/citologia , Tirosina/análogos & derivados , Tirosina/metabolismoRESUMO
The lck gene encodes a lymphocyte-specific protein tyrosine kinase of the nonreceptor type that is implicated in signal transduction pathways emanating from the CD4 and CD8 coreceptors. Previous studies also support a role for p56lck in regulating T cell receptor beta gene rearrangements and, more generally, thymocyte development. Here we report that a mutant form of p56lck, which is incapable of interacting with CD4 or CD8, behaves indistinguishably from association-competent p56lck with respect to its ability to affect thymocyte maturation. The effects of p56lck remained specific in that the closely related src-family kinase p59hck was incapable of substituting for p56lck in arresting beta locus gene rearrangements. These data support the view that src-family kinases perform highly specialized and often nonoverlapping functions in hematopoietic cells, and that p56lck acts independently of its association with CD4 and CD8 to regulate thymocyte development.
Assuntos
Antígenos CD4/fisiologia , Antígenos CD8/fisiologia , Proteínas Tirosina Quinases/fisiologia , Proteínas Proto-Oncogênicas/fisiologia , Linfócitos T/fisiologia , Animais , Rearranjo Gênico da Cadeia beta dos Receptores de Antígenos dos Linfócitos T , Proteína Tirosina Quinase p56(lck) Linfócito-Específica , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Transgênicos , Proteínas Proto-Oncogênicas/genética , Receptores de Interleucina-2/fisiologia , Linfócitos T/imunologiaRESUMO
Maturational changes at the CD4(-)CD8(-) double negative (DN) to CD4(+)CD8(+) double positive (DP) transition are dependent on signals generated via the pre-T cell receptor (TCR) and the nonreceptor protein tyrosine kinase p56(lck) (Lck). How Lck activities are stimulated or relayed after pre-TCR formation remains obscure. Our structure-function mapping of Lck thymopoietic properties reveals that the noncatalytic domains of Lck are specialized to signal efficient cellular expansion at DN to DP transition. Moreover, although substitution of the Lck catalytic domain with FynT sequences minimally impacts DP development, single positive thymocytes are most efficiently produced in the presence of kinases containing both the NH(2)-terminal and catalytic regions of Lck. These findings demonstrate that the Lck structure is uniquely adapted to mediate signals at both major transitions in thymopoiesis.
Assuntos
Linfócitos T CD4-Positivos/imunologia , Linfócitos T CD8-Positivos/imunologia , Proteína Tirosina Quinase p56(lck) Linfócito-Específica/metabolismo , Proteínas Proto-Oncogênicas/metabolismo , Receptores de Antígenos de Linfócitos T alfa-beta/fisiologia , Timo/imunologia , Animais , Domínio Catalítico , Diferenciação Celular , Proteína Tirosina Quinase p56(lck) Linfócito-Específica/deficiência , Proteína Tirosina Quinase p56(lck) Linfócito-Específica/genética , Camundongos , Camundongos Knockout , Camundongos Transgênicos , Proteínas Proto-Oncogênicas/deficiência , Proteínas Proto-Oncogênicas/genética , Proteínas Proto-Oncogênicas c-fyn , Receptores de Antígenos de Linfócitos T alfa-beta/deficiência , Receptores de Antígenos de Linfócitos T alfa-beta/genética , Proteínas Recombinantes de Fusão/imunologia , Transdução de Sinais , Timo/citologia , TransfecçãoRESUMO
In the mouse and human, mRNA transcripts encoding the lymphocyte-specific protein tyrosine kinase p56lck are derived from two separate promoters resulting in heterogeneity in the 5' untranslated region sequence. The proximal promoter lies just 5' to the coding region for the gene and is active only in thymocytes. In contrast, the distal promoter lies 34 kilobases (kb) 5' in the human, and is active both in thymocytes and mature peripheral T cells. As previously reported, transgenic mice bearing functional proximal promoter sequence juxtaposed with the SV40 large T antigen gene invariably develop lymphoid tumors confined to the thymus. In the current work, transgenic mice bearing a 2.6-kb fragment of the human distal promoter fused to the SV40 large T antigen gene express large T antigen in thymocytes and in peripheral lymphoid cells, and develop tumors of both the thymus and the peripheral lymphoid organs. The ability of the human distal promoter to function appropriately in transgenic mice is consistent with the strong similarity observed between the mouse and human distal promoter sequences. With the exception of a single short interval that serves as a target for binding of nuclear factors, significant sequence similarity is not seen when the distal and proximal promoter sequences are compared. Hence, developmentally regulated, lineage-specific transcription of the lck gene is mediated by distinct promoter sequences that appear to be capable of functioning independently.
Assuntos
Regulação da Expressão Gênica/genética , Proteínas Tirosina Quinases/genética , Linfócitos T/metabolismo , Animais , Antígenos Transformantes de Poliomavirus/genética , Sequência de Bases , Clonagem Molecular , DNA/metabolismo , Humanos , Proteína Tirosina Quinase p56(lck) Linfócito-Específica , Tecido Linfoide/metabolismo , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Transgênicos , Dados de Sequência Molecular , Proteínas Nucleares/metabolismo , Sondas de Oligonucleotídeos , Regiões Promotoras Genéticas/genéticaRESUMO
Metal macrocycles are among the most important catalytic systems in electrocatalysis and biocatalysis owing to their rich redox chemistry. Precise understanding of the redox behavior of metal macrocycles in operando is essential for fundamental studies and practical applications of this catalytic system. Here we present electrochemical data for the representative iron phthalocyanine (FePc) in both aqueous and nonaqueous media coupled with in situ Raman and X-ray absorption analyses to challenge the traditional notion of the redox transition of FePc at the low potential end in aqueous media by showing that it arises from the redox transition of the ring. Our data unequivocally demonstrate that the electron is shuttled to the Pc ring via the Fe(II)/Fe(I) redox center. The Fe(II)/Fe(I) redox transition of FePc in aqueous media is indiscernible by normal spectroscopic methods owing to the lack of a suitable axial ligand to stabilize the Fe(I) state.
RESUMO
Based on a simple thermodynamic analysis, we show that iodide-mediated electrochemical decomposition of lithium hydroxide (LiOH) likely occurs through a different mechanism than that proposed by Liu et al (Research Article, 30 October 2015, p. 530). The mismatch in thermodynamic potentials for iodide/triiodide (I(-)/I3 (-)) redox and O2 evolution from LiOH implies a different active iodine/oxygen electrochemistry on battery charge. It is therefore possible that the system described in Liu et al may not form the basis for a rechargeable lithium-oxygen (Li-O2) battery.
RESUMO
The distribution and quantity of cellular signaling elements influence response patterns to a variety of stimuli. As protein tyrosine phosphorylation is a requisite event induced by a majority of surface receptors, and protein tyrosine kinases of the src-family (src-PTKs) act as proximal transducers for many hematopoietic receptors, we have designed a quantitative RT-PCR assay to measure src-family PTK expression during critical stages of lymphocyte ontogeny. With this assay we demonstrate that the distal promoter element regulating expression of lck, a src-PTK essential for T-cell development and activation, is similarly regulated during ontogeny of T and B cells. However, lck transcript abundance is drastically reduced in B lineage cells, suggesting that transcriptional elements influencing lck promoter activity are modulated in these cells. Moreover, although transcripts encoding the src-PTK fyn accumulate at 0.1% of lck mRNA levels in thymocytes, diminished activity of the lck distal promoter in the B-cell background brings lck and fyn transcript levels to near equivalence in this population. Importantly, transcripts arising from the lck distal promoter element and the fyn locus are similarly upregulated during developmental transitions associated with antigen-receptor expression in both B and T cells. These findings suggest that although the magnitude of lck and fyn expression is differentially regulated in B and T cells, expression at these loci is similarly developmentally programmed during ontogeny of both lymphocyte lineages.
Assuntos
Linfócitos/enzimologia , Quinases da Família src/genética , Animais , Linfócitos B/citologia , Linfócitos B/enzimologia , Linfócitos B/imunologia , Primers do DNA/genética , Feminino , Feto/citologia , Feto/imunologia , Feto/metabolismo , Regulação da Expressão Gênica no Desenvolvimento , Hematopoese , Proteína Tirosina Quinase p56(lck) Linfócito-Específica/genética , Linfócitos/citologia , Linfócitos/imunologia , Camundongos , Camundongos Endogâmicos C57BL , Fator 1 de Elongação de Peptídeos/genética , Fator 1 de Elongação de Peptídeos/normas , Reação em Cadeia da Polimerase/métodos , Reação em Cadeia da Polimerase/normas , Gravidez , Regiões Promotoras Genéticas , Proteínas Proto-Oncogênicas/genética , Proteínas Proto-Oncogênicas c-fyn , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Padrões de Referência , Linfócitos T/citologia , Linfócitos T/enzimologia , Linfócitos T/imunologiaRESUMO
Energy densities of Li ion batteries, limited by the capacities of cathode materials, must increase by a factor of 2 or more to give all-electric automobiles a 300 mile driving range on a single charge. Battery chemical couples with very low equivalent weights have to be sought to produce such batteries. Advanced Li ion batteries may not be able to meet this challenge in the near term. The state-of-the-art of Li ion batteries is discussed, and the challenges of developing ultrahigh energy density rechargeable batteries are identified. Examples of ultrahigh energy density battery chemical couples include Li/O2, Li/S, Li/metal halide, and Li/metal oxide systems. Future efforts are also expected to involve all-solid-state batteries with performance similar to their liquid electrolyte counterparts, biodegradable batteries to address environmental challenges, and low-cost long cycle-life batteries for large-scale energy storage. Ultimately, energy densities of electrochemical energy storage systems are limited by chemistry constraints.
Assuntos
Linfócitos/análise , Proteínas Tirosina Quinases/genética , Proteínas Proto-Oncogênicas/genética , Proto-Oncogenes , Regulação da Expressão Gênica , Rearranjo Gênico , Humanos , Linfoma/etiologia , Proteínas Tirosina Quinases/análise , Proteínas Proto-Oncogênicas/análise , Proteínas Proto-Oncogênicas pp60(c-src)RESUMO
The regulation of antibody class expression has been an active and controversial area of research for many years. Although it is well established that T cells influence which antibody isotypes are produced during an immune response, their exact mode of action has not been delineated. In this review Judy Teale and Kristin Abraham briefly summarize current understanding of isotype regulation and describe the T cells and/or their factors which may provide the biological signals that induce the immunoglobulin class switch.
RESUMO
Mice infected with the parasite Mesocestoides corti undergo a polyclonal antibody response that results in a hypergammaglobulinemia restricted to the IgM and IgG1 isotypes. It was found that a similar restriction to IgM and IgG1 could be observed in an in vitro lymphocyte culture system providing that the source of helper T cells was from infected animals. In order to characterize the helper T cells responsible for the restriction, helper T cell clones were generated. Attempts to obtain isotype-restricting helper T cell clones by using the intact, nonviable organism were unsuccessful in that these T cell clones promoted multiple antibody class expression. However, two types of CD4+ (cluster designation) T cell clones were generated by cultivation on the live organism that appeared relevant to the observed restriction. These T cells did not function as conventional carrier-specific helper T cells. Instead, they were shown to regulate T-dependent responses to 2,4-dinitrophenyl-keyhole limpet hemocyanin by 2,4-dinitrophenyl-specific B cells and keyhole limpet hemocyanin-primed T cells derived from uninfected mice. The helper phenotype of one regulatory clone enhanced the IgG1 response, whereas the other phenotype inhibited the production of the other non-IgM isotypes tested. It is concluded that the activities of these two prototype regulatory T cell clones may predominate in infected animals resulting in the IgM, IgG1 dominance of the antibody response.
Assuntos
Formação de Anticorpos , Cestoides/imunologia , Infecções por Cestoides/imunologia , Isotipos de Imunoglobulinas/imunologia , Mesocestoides/imunologia , Linfócitos T Auxiliares-Indutores/imunologia , Animais , Antígenos de Diferenciação de Linfócitos T/análise , Linhagem Celular , Dinitrobenzenos/imunologia , Imunidade Celular , Imunoglobulina G/biossíntese , Imunoglobulina M/biossíntese , Cooperação Linfocítica , CamundongosRESUMO
Mice infected with the parasite Mesocestoides corti produce a vigorous antibody response that is restricted to the IgM and IgG1 heavy chain classes. The isotypic restriction observed is apparently associated with active infection and is not a unique characteristic of responses to M. corti antigens. Thus, animals immunized with intact but nonviable parasites respond with the production of a variety of antibody isotypes in addition to IgM and IgG1. To delineate immunoregulatory mechanisms involved in the isotypic restriction of antibody responses to M. corti, an in vitro lymphocyte suspension culture was established. The data indicate that there are two cell subsets in the spleens of infected mice that contribute to an overall suppression of the in vitro antibody response. Thus, both Lyt-2+ cells and G-10-adherent cells must be removed to maximize antibody production. However, the anti-parasite response obtained in vitro after depletion of Lyt-2+ cells and G-10-adherent cells is restricted to the IgM and IgG1 isotypes as observed in vivo, indicating that suppression is not actively involved in the IgM, IgG1 dominance of the response. The cellular regulation associated with this restriction was then studied by using isolated helper T cells derived from parasite-infected animals to stimulate B cells from uninfected animals. The antibody produced was again restricted to IgM and IgG1, indicating that the helper T cells were regulating the preferential expression of the IgM and IgG1 antibody classes.
Assuntos
Antígenos de Helmintos/imunologia , Cestoides/imunologia , Infecções por Cestoides/imunologia , Tolerância Imunológica , Isotipos de Imunoglobulinas/imunologia , Mesocestoides/imunologia , Animais , Antígenos Ly/análise , Imunoglobulina G/biossíntese , Imunoglobulina M/biossíntese , Macrófagos/imunologia , Camundongos , Linfócitos T Auxiliares-Indutores/imunologia , Linfócitos T Reguladores/imunologiaRESUMO
Previous studies suggest that p56(lck) activity influences thymocyte development at a stage prior to TCR alphabeta expression. Transgenic mice that express high levels of p56(lck) activity during thymopoiesis develop thymic lymphomas consisting of cells with immature surface phenotypes. We have utilized cell lines derived from lck-induced thymic tumors to define biochemical pathways regulated by p56(lck) activity in immature thymocytes. Here we report that components of the Ras/Raf/MAPK pathway are constitutively activated in these lck-transformed immature thymoblasts. p56(lck) utilizes Shc and Grb2 adaptors to mediate activation of p21(ras) in the thymoblast lines by promoting tyrosine phosphorylation of the Shc protein and constitutive interaction between Shc and Grb2. The putative guanine nucleotide exchange factor p95(vav) is also maintained in constitutively tyrosine phosphorylated form as a result of elevated Lck activity. One target of activated Ras, the Raf-1 kinase, is hyperphosphorylated and downstream targets of activated Raf-1, Erk1 and Erk2, are hyperphosphorylated and activated in Lck-transformed thymocytes. Forskolin treatment reverses Raf-1 hyperphosphorylation in the cells and inhibits proliferation by blocking G1/S transition. In contrast, conventional protein tyrosine kinase inhibitors block proliferation by arresting Lck thymoblasts at G2/M. Lck-mediated stimulation of the Ras/Raf/MAPK pathway is also required to maintain cell viability by preventing programmed cell death. In summary, p56(lck) activity stimulates G1/S transition in immature thymoblasts and maintains cell viability via transduction of constitutive activation signals downstream to components of the Ras/Raf/MAPK pathway.
Assuntos
Proteínas Quinases Dependentes de Cálcio-Calmodulina/metabolismo , Proteínas de Ciclo Celular , Ativação Linfocitária , Proteínas Proto-Oncogênicas/metabolismo , Transdução de Sinais/imunologia , Linfócitos T/imunologia , Timo/citologia , Proteínas ras/metabolismo , Quinases da Família src/imunologia , Animais , Apoptose/imunologia , Proteínas Quinases Dependentes de Cálcio-Calmodulina/fisiologia , Divisão Celular/imunologia , Divisão Celular/fisiologia , AMP Cíclico/metabolismo , AMP Cíclico/fisiologia , Proteína Tirosina Quinase p56(lck) Linfócito-Específica , Linfoma , Camundongos , Camundongos Transgênicos , Proteínas Serina-Treonina Quinases/imunologia , Proteínas Serina-Treonina Quinases/metabolismo , Proteínas Proto-Oncogênicas/imunologia , Proteínas Proto-Oncogênicas c-raf , Proteínas Proto-Oncogênicas c-vav , Transdução de Sinais/fisiologia , Linfócitos T/citologia , Linfócitos T/fisiologia , Timo/crescimento & desenvolvimento , Células Tumorais Cultivadas , Proteínas ras/imunologiaRESUMO
Infection of BALB/c mice with Mesocestoides corti results in a chronic infection with a pronounced splenomegaly and hypergammaglobulinemia. A prominent feature of this infection is that the vast majority of serum immunoglobulin produced is restricted to IgG1 and IgM. As much as 30-fold increases in serum IgG1 levels have been noted. To ascertain whether, as a result of infection, the resident B cell pool is committed to IgG1, B cells from infected animals were tested for their ability to produce various isotypes after stimulation. In one series of experiments, B cells from normal and infected animals were used as donor cells in the splenic fragment assay. The results show that the frequency of 2,4-dinitrophenyl-specific and phosphorylcholine-specific B cells remains unaltered in infected animals compared to controls. Importantly, the hapten-specific B cell clones induced were found to express multiple isotypes. These results demonstrate that the nonactivated B cell pool in spleens of infected mice is not committed to IgG1 and IgM production.
Assuntos
Linfócitos B/imunologia , Infecções por Cestoides/imunologia , Isotipos de Imunoglobulinas/imunologia , Animais , Formação de Anticorpos , Linfócitos T CD4-Positivos/imunologia , Dinitrobenzenos/imunologia , Interleucina-4/biossíntese , Ativação Linfocitária , Linfocinas/biossíntese , Mesocestoides/imunologia , Camundongos , Camundongos Endogâmicos BALB C , Fosforilcolina/imunologiaRESUMO
The variable region genes of the T cell receptor (TCR) alpha and beta chains are assembled by somatic recombination of separate germline elements. During thymocyte development, gene rearrangements display both an ordered progression, with beta chain formation preceding alpha chain, and allelic exclusion, with each cell containing a single functional beta chain rearrangement. Although considerable evidence supports the view that the individual loci are regulated independently, signaling molecules that may participate in controlling TCR gene recombination remain unidentified. Here we report that the lymphocyte-specific protein tyrosine kinase p56lck, when overexpressed in developing thymocytes, provokes a reduction in V beta--D beta rearrangement while permitting normal juxtaposition of other TCR gene segments. Our data support a model in which p56lck activity impinges upon a signaling process that ordinarily permits allelic exclusion at the beta-chain locus.
Assuntos
Rearranjo Gênico da Cadeia beta dos Receptores de Antígenos dos Linfócitos T , Proteínas Tirosina Quinases/fisiologia , Animais , Sequência de Bases , Northern Blotting , DNA de Cadeia Simples , Citometria de Fluxo , Immunoblotting , Proteína Tirosina Quinase p56(lck) Linfócito-Específica , Camundongos , Camundongos Transgênicos , Dados de Sequência Molecular , Reação em Cadeia da Polimerase , Proteínas Tirosina Quinases/genética , Receptores de Antígenos de Linfócitos T/genética , Timo/citologia , Transcrição GênicaRESUMO
Engagement of the clonotypic antigen receptor (TCR) on T lymphocytes provokes an activation response leading to cell proliferation and lymphokine secretion. To examine the molecular basis of T cell signaling, we generated transgenic animals in which a lymphocyte-specific nonreceptor protein-tyrosine kinase p59fyn(T) is 20-fold overexpressed in developing T lineage cells. Thymocytes from these mice, analyzed using both cellular and biochemical assays, were remarkably hyperstimulable. Moreover, the responsiveness of normal thymocytes to TCR-derived signals correlated well with the extent to which p59fyn was expressed in these cells. Overexpression of a catalytically inactive form of p59fyn substantially inhibited TCR-mediated activation in otherwise normal thymocytes. These effects are unique to p59fyn; overexpression of a closely related T cell-specific tyrosine kinase, p56lck, elicits dramatically different phenotypes. Our results suggest that p59fyn is a critically important component of the TCR signal transduction apparatus.