Hot Papers

M.H. Siegelman, M. van de Rijn, I.L. Weissman, "Mouse lymph node homing receptors cDNA clone encodes a glycoprotein revealing tandem interaction domains," Science, 243, 1165-72, 3 March 1989. Mark Siegelman (Stanford University Medical Center, Calif.): "Our characterization of the lymph node-specific homing receptor protein showed it to be composed of a core protein with complex and novel posttrans- lational modifications. Our cloning of the cDNA encoding the core polypeptide revealed an entirely new class of adhesion molecule with a remarkable protein design. This design consists of a tandem array of three independent protein domains brought together to form the homing receptor protein. These domains are a lectin domain, an epidermal growth factor-like domain, and two similar repeats of a motif present in a number of proteins that regulate the complement cascade. The unique juxtaposition of these protein segments recruited into a single molecule provides a rich model for study of protein- structure relationships. "Because lymphocyte homing receptors reside at the interface between a cell's dynamic circulating phase and its relatively sessile state outside of the bloodstream, the implications for participation in both normal and neoplastic processes are quite broad. The regulation of these receptors has roles in the patterns of lymphoid and, perhaps, nonlymphoid metastasis; in the recruitment of cells to inflammatory sites; and, likely, in the determination of cell migration pathways in the adult as well as during embryogenesis." K.R. Auger, L.A. Serunian, S.P. Soltoff, P. Libby, L.C. Cantley, "PDGF-dependent tyrosine phosphorylation stimulates production of novel polyphosphoinositides in intact cells," Cell, 57, 167-75, 7 April 1989. Kurt Auger (Tufts University School of Medicine, Boston): "This paper proposes a new growth factor signal transduction pathway. The canonical phosphatidylinositol pathway involves phosphor- ylation of phosphatidylinositol at the 4 and 5 positions of the inositol ring followed by hydrolysis to produce the second messengers inositol-1,4,5- trisphosphate and diacylgly- cerol. This paper shows that the platelet-derived growth factor stimulates an enzyme that phosphorylates the 3 position of the inositol ring to produce a series of novel polyphos- phoinositides that are not in the canonical pathway. The phosphatidylinositol 3-kinase was discovered because of its physical association with oncogenic protein-tyrosine kinases, and mutational studies indicate that activation of this enzyme is essential for growth and transforming abilities of several protein-tyrosine kinases." P.A. Marsden, N.R. Danthuluri, B.M. Brenner, B.J. Ballermann, T.A. Brock, "Endothelin action on vascular smooth muscle involves inositol triphosphate and calcium mobilization," Biochemical and Biophysical Research Communications, 158, 86-93, 16 January 1989. Philip A. Marsden (Harvard Medical School, Boston): "Endothelin-1 is one of the most potent vasoconstrictors yet studied. The contribution of this vasomediator to the physiologic and pathophysiologic control of the circulation is currently of great interest. This paper was one of the first to describe the early membrane signaling events by which endothelin-1 induces vasoconstriction. Endothelin-1 induced the concentration- dependent increase of cytosolic free calcium concentration, [Ca2+]i, in cultured vascular smooth muscle cells, even in the absence of extracellular Ca2+. Furthermore, endothelin increased the transmembrane flux of 45Ca2+. Measurement of inositol phosphates in [3H]-myoinositol-labeled vascular smooth muscle cells showed that endothelin induced rapid, transient formation of inositol trisphosphate. Taken together, the observations that changes in [Ca2+]i did not depend on extracellular Ca2+ and that endothelin induced the formation of inositol trisphosphates in vascular smooth muscle cells suggest that activation of phospholipase C is one of the early membrane signaling events following endothelin/receptor interaction." C. Murre, P. Schonleber McCaw, D. Baltimore, "A new DNA binding and dimerization motif in immunoglobulin enhancer binding, daughterless, MyoD, and myc proteins," Cell, 56, 777-83, 10 March 1989. Cornelis Murre (Whitehead Institute for Biomedical Research, Cambridge, Mass.): "When we cloned cDNAs for proteins that bound to the kE2 DNA motif in the intron enhancer of k immunoglobulin light chain genes, we realized that they helped to define a new class of DNA-binding proteins. These proteins have a dimerization motif apparently made of two amphipathic à-helices separated by a variable loop leading to their designation as helix-loop-helix, or HLH, proteins. They can homodimerize or hetero- dimerize. Because the proteins with this motif include a number of key differentiation factors and also a number of oncogenes, the identification of this dimerization motif has helped progress in a number of fields."

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