Catálogo de publicaciones - revistas

<jats:p> Signal transmission by many cell surface receptors results in the activation of phosphoinositide (PI) 3-kinases that phosphorylate the 3′ position of polyphosphoinositides. From a screen for mouse proteins that bind phosphoinositides, the protein GRP1 was identified. GRP1 binds phosphatidylinositol-3,4,5-trisphosphate [PtdIns(3,4,5)P <jats:sub>3</jats:sub> ] through a pleckstrin homology (PH) domain and displays a region of high sequence similarity to the yeast Sec7 protein. The PH domain of the closely related protein cytohesin-1, which, through its Sec7 homology domain, regulates integrin β2 and catalyzes guanine nucleotide exchange of the small guanine nucleotide-binding protein ARF1, was also found to specifically bind PtdIns(3,4,5)P <jats:sub>3</jats:sub> . GRP1 and cytohesin-1 appear to connect receptor-activated PI 3-kinase signaling pathways with proteins that mediate biological responses such as cell adhesion and membrane trafficking. </jats:p>

<jats:p> The transcription factor NF-AT responds to Ca <jats:sup>2+</jats:sup> -calcineurin signals by translocating to the nucleus, where it participates in the activation of early immune response genes. Calcineurin dephosphorylates conserved serine residues in the amino terminus of NF-AT, resulting in nuclear import. Purification of the NF-AT kinase revealed that it is composed of a priming kinase activity and glycogen synthase kinase-3 (GSK-3). GSK-3 phosphorylates conserved serines necessary for nuclear export, promotes nuclear exit, and thereby opposes Ca <jats:sup>2+</jats:sup> -calcineurin signaling. Because GSK-3 responds to signals initiated by Wnt and other ligands, NF-AT family members could be effectors of these pathways. </jats:p>

<jats:p>Natural populations of guppies were subjected to an episode of directional selection that mimicked natural processes. The resulting rate of evolution of age and size at maturity was similar to rates typically obtained for traits subjected to artificial selection in laboratory settings and up to seven orders of magnitude greater than rates inferred from the paleontological record. Male traits evolved more rapidly than female traits largely because males had more genetic variation upon which natural selection could act. These results are considered in light of the ongoing debate about the importance of natural selection versus other processes in the paleontological record of evolution.</jats:p>

<jats:p> Neuroendocrine hormones of the hypothalamus-pituitary-thyroid axis can exert positive or negative immunoregulatory effects on intestinal lymphocytes. Small intestine epithelial cells were found to express receptors for thyrotropin-releasing hormone (TRH) and to be a primary source of intestine-derived thyroid-stimulating hormone (TSH). The gene for the TSH receptor (TSH-R) was expressed in intestinal T cells but not in epithelial cells, which suggested a hormone-mediated link between lymphoid and nonhematopoietic components of the intestine. Because mice with congenitally mutant TSH-R ( <jats:italic>hyt</jats:italic> / <jats:italic>hyt</jats:italic> mice) have a selectively impaired intestinal T cell repertoire, TSH may be a key immunoregulatory mediator in the intestine. </jats:p>

<jats:p>The cerebellum traditionally has been viewed as a neural device dedicated to motor control. Although recent evidence shows that it is involved in nonmotor operations as well, an important question is whether this involvement is independent of motor control and motor guidance. Functional magnetic resonance imaging was used to demonstrate that attention and motor performance independently activate distinct cerebellar regions. These findings support a broader concept of cerebellar function, in which the cerebellum is involved in diverse cognitive and noncognitive neurobehavioral systems, including the attention and motor systems, in order to anticipate imminent information acquisition, analysis, or action.</jats:p>

<jats:p> Mapping of homozygous deletions on human chromosome 10q23 has led to the isolation of a candidate tumor suppressor gene, <jats:italic>PTEN</jats:italic> , that appears to be mutated at considerable frequency in human cancers. In preliminary screens, mutations of <jats:italic>PTEN</jats:italic> were detected in 31% (13/42) of glioblastoma cell lines and xenografts, 100% (4/4) of prostate cancer cell lines, 6% (4/65) of breast cancer cell lines and xenografts, and 17% (3/18) of primary glioblastomas. The predicted <jats:italic>PTEN</jats:italic> product has a protein tyrosine phosphatase domain and extensive homology to tensin, a protein that interacts with actin filaments at focal adhesions. These homologies suggest that <jats:italic>PTEN</jats:italic> may suppress tumor cell growth by antagonizing protein tyrosine kinases and may regulate tumor cell invasion and metastasis through interactions at focal adhesions. </jats:p>