The role of tyrosine-specific phosphorylation in v-fms-mediated transformation was examined by immunoblotting techniques together with a high-affinity antibody that is specific for phosphotyrosine. This antiphosphotyrosine antibody detected phosphorylated tyrosine residues on the gp140v-fms molecule, but not gP180v-fms or gp120v-fms, in v-fms-transformed cells. This antibody also identified a number of cellular proteins that were either newly phosphorylated on tyrosine residues or showed enhanced phosphorylation on tyrosine residues as a result of v-fms transformation. However, the substrates of the v-fms-induced tyrosine kinase activity were not the characterized pp60v-src substrates. The phosphorylation of some of these cellular proteins and of the gp140fms molecule was found to correlate with the ability of v-fms/c-fms hybrids to transform cells. In addition, immunoblotting with the phosphotyrosine antibody allowed a comparison to be made of the substrates phosphorylated on tyrosine residues in various transformed cell lines. This study indicates that the pattern of tyrosine phosphorylation in v-fms-transformed cells is strikingly similar to that in v-sis-transformed cells.
ABSTRACT Sperm of the nematode, Ascaris suum, are amoeboid cells that do not require actin or myosin to crawl over solid substrata. In these cells, the role usually played by actin has been taken over by major sperm protein (MSP), which assembles into filaments that pack the sperm pseudopod. These MSP filaments are organized into multi-filament arrays called fiber complexes that flow centripetally from the leading edge of the pseudopod to the cell body in a pattern that is intimately associated with motility. We have characterized structurally a hierarchy of helical assemblies formed by MSP. The basic unit of the MSP cytoskeleton is a filament formed by two subfilaments coiled around one another along right-handed helical tracks. In vitro, higher-order assemblies (macrofibers) are formed by MSP filaments that coil around one another in a left-handed helical sense. The multi-filament assemblies formed by MSP in vitro are strikingly similar to the fiber complexes that characterize the sperm cytoskeleton. Thus, self-association is an intrinsic property of MSP filaments that distinguishes these fibers from actin filaments. The results obtained with MSP help clarify the roles of different aspects of the actin cytoskeleton in the generation of loco-motion and, in particular, emphasize the contributions made by vectorial assembly and filament bundling.
<div>Abstract<p>A common outcome of androgen deprivation in prostate cancer therapy is disease relapse and progression to castration-resistant prostate cancer (CRPC) via multiple mechanisms. To gain insight into the recent clinical findings that highlighted genomic alterations leading to hyperactivation of PI3K, we examined the roles of the commonly expressed p110 catalytic isoforms of PI3K in a murine model of Pten-null invasive CRPC. While blocking p110α had negligible effects in the development of Pten-null invasive CRPC, either genetic or pharmacologic perturbation of p110β dramatically slowed CRPC initiation and progression. Once fully established, CRPC tumors became partially resistant to p110β inhibition, indicating the acquisition of new dependencies. Driven by our genomic analyses highlighting potential roles for the p110β/RAC/PAK1 and β-catenin pathways in CRPC, we found that combining p110β with RAC/PAK1 or tankyrase inhibitors significantly reduced the growth of murine and human CRPC organoids <i>in vitro</i> and <i>in vivo</i>. Because p110β activity is dispensable for most physiologic processes, our studies support novel therapeutic strategies both for preventing disease progression into CRPC and for treating CRPC.</p>Implications:<p>This work establishes p110β as a promising target for preventing the progression of primary PTEN-deficient prostate tumors to CRPC, and for treating established CRPC in combination with RAC/PAK1 or tankyrase inhibitors.</p></div>
Recent work has shown that ablation of p110β, but not p110α, markedly impairs tumorigenesis driven by loss of phosphatase and tensin homolog (PTEN) in the mouse prostate. Other laboratories have reported complementary data in human prostate tumor lines, suggesting that p110β activation is necessary for tumorigenesis driven by PTEN loss. Given the multiple functions of PTEN, we wondered if p110β activation also is sufficient for tumorigenesis. Here, we report that transgenic expression of a constitutively activated p110β allele in the prostate drives prostate intraepithelial neoplasia formation. The resulting lesions are similar to, but are clearly distinct from, the ones arising from PTEN loss or Akt activation. Array analyses of transcription in multiple murine prostate tumor models featuring PI3K/AKT pathway activation allowed construction of a pathway signature that may be useful in predicting the prognosis of human prostate tumors.
?Que podemos aprender los seres humanos? ?Como sabremos transmitirlo a otros? ?Podemos ensenar a los demas a desarrollar sus capacidades con eficacia? ?Como aprenderemos a hacer mas, a hacerlo mejor y mas rapidamente? ?Como hacemos lo que hacemos y por que? ?Que somos capaces de realizar y que desconocemos todavia?
Cuatro psicologias aplicadas la educacion trata de responder a estos interrogantes y provocar otros nuevos desde la perspectiva de la psicologia educacional. Es una seleccion de escritos tan importantes como los de Anna Freud, Carl Jung, Erik Erikson, A.S. Neill, Carl Rogers, Abrahm Maslow, Aldous Huxley, Arthur Koestler, etc, que aportarn una profundizacion en la conducta humana dentro del marco educativa y constituyen un elenco valioso y bien organizado de los estudios existentes sobre el aprendizaje.
En su estructura, la obra presenta en bloques separados. Cuatro psicologias —freudiana y transpersonal en el primer volumen, behaviorista y humanistica en el segundo— en algunas de sus aplicaciones pedagogicas. Cada bloque esta ordenado de modo que permite la facil captacion de los conceptos fundamentales de la escuela psicologica correspondiente y viene precedido de una introduccion en la que Roberts ofrece una vision de conjunto de cada una de las psicologias.
La gran cohesion interna de la obra, junto a la amplitud que le viene de las distintas cuestiones que suscita, las diferentes formas de pensar que ofrece y los diversos aspectos del ser humano que aborda, hacen de ella un libro imprescindible para los estudiantes y una gran ayuda para profesores, padres y educadores empenados en la comprension y perfeccionamiento de nuestros sistemas educativos actuales.
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