An Activating Mutation in sos-1 Identifies Its Dbl Domain as a Critical Inhibitor of the Epidermal Growth Factor Receptor Pathway during Caenorhabditis elegans Vulval Development

Proper regulation of receptor tyrosine kinase (RTK)-Ras-mitogen-activated protein kinase (MAPK) signaling pathways is critical for normal development and the prevention of cancer. SOS is a dual-function guanine nucleotide exchange factor (GEF) that catalyzes exchange on Ras and Rac. Although the physiologic role of SOS and its CDC25 domain in RTK-mediated Ras activation is well established, the in vivo function of its Dbl Rac GEF domain is less clear. We have identified a novel gain-of-function missense mutation in the Dbl domain of Caenorhabditis elegans SOS-1 that promotes epidermal growth factor receptor (EGFR) signaling in vivo. Our data indicate that a major developmental function of the Dbl domain is to inhibit EGF-dependent MAPK activation. The amount of inhibition conferred by the Dbl domain is equal to that of established trans-acting inhibitors of the EGFR pathway, including c-Cbl and RasGAP, and more than that of MAPK phosphatase. In conjunction with molecular modeling, our data suggest that the C. elegans mutation, as well as an equivalent mutation in human SOS1, activates the MAPK pathway by disrupting an autoinhibitory function of the Dbl domain on Ras activation. Our work suggests that functionally similar point mutations in humans could directly contribute to disease

Generalized Pseudopotentials for Higher Partial Wave Scattering

We derive a generalized zero-range pseudopotential applicable to all partial wave solutions to the Schroedinger equation based on a delta-shell potential in the limit that the shell radius approaches zero. This properly models all higher order multipole moments not accounted for with a monopolar delta function at the origin, as used in the familiar Fermi pseudopotential for s-wave scattering. By making the strength of the potential energy dependent, we derive self-consistent solutions for the entire energy spectrum of the realistic potential. We apply this to study two particles in an isotropic harmonic trap, interacting through a central potential, and derive analytic expressions for the energy eigenstates and eigenvalues.Comment: RevTeX 4 pages, 1 figure, final published versio

Chondrule formation, metamorphism, brecciation, an important new primary chondrule group, and the classification of chondrules

The recently proposed compositional classification scheme for meteoritic chondrules divides the chondrules into groups depending on the composition of their two major phases, olivine (or pyroxene) and the mesostasis, both of which are genetically important. The scheme is here applied to discussions of three topics: the petrographic classification of Roosevelt County 075 (the least-metamorphosed H chondrite known), brecciation (an extremely important and ubiquitous process probably experienced by greater than 40% of all unequilibrated ordinary chondrites), and the group A5 chondrules in the least metamorphosed ordinary chondrites which have many similarities to chondrules in the highly metamorphosed 'equilibrated' chondrites. Since composition provides insights into both primary formation properties of the chondruies and the effects of metamorphism on the entire assemblage it is possible to determine the petrographic type of RC075 as 3.1 with unique certainty. Similarly, the near scheme can be applied to individual chondrules without knowledge of the petrographic type of the host chondrite, which makes it especially suitable for studying breccias. Finally, the new scheme has revealed the existence of chondrules not identified by previous techniques and which appear to be extremely important. Like group A1 and A2 chondrules (but unlike group B1 chondrules) the primitive group A5 chondruies did not supercool during formation, but unlike group A1 and A2 chondrules (and like group B1 chondrules) they did not suffer volatile loss and reduction during formation. It is concluded that the compositional classification scheme provides important new insights into the formation and history of chondrules and chondrites which would be overlooked by previous schemes