The Raf-1 kinase is an important signaling molecule, functioning in the Ras pathway to transmit mitogenic, differentiative, and oncogenic signals to the downstream kinases MEK and ERK. Because of its integral role in cell signaling, Raf-1 activity must be precisely controlled. Previous studies have shown that phosphorylation is required for Raf-1 activation, and here, we identify six phosphorylation sites that contribute to the downregulation of Raf-1 after mitogen stimulation. Five of the identified sites are proline-directed targets of activated ERK, and phosphorylation of all six sites requires MEK signaling, indicating a negative feedback mechanism. Hyperphosphorylation of these six sites inhibits the Ras/Raf-1 interaction and desensitizes Raf-1 to additional stimuli. The hyperphosphorylated/desensitized Raf-1 is subsequently dephosphorylated and returned to a signaling-competent state through interactions with the protein phosphatase PP2A and the prolyl isomerase Pin1. These findings elucidate a critical Raf-1 regulatory mechanism that contributes to the sensitive, temporal modulation of Ras signaling.

[1] We investigate the evolution of the properties of planetary period magnetic field oscillations observed by the Cassini spacecraft in Saturn's magnetosphere over the interval from late 2004 to early 2011, spanning equinox in mid-2009. Oscillations within the inner quasi-dipolar region (L ≤ 12) consist of two components of close but distinct periods, corresponding essentially to the periods of the northern and southern Saturn kilometric radiation (SKR) modulations. These give rise to modulations of the combined amplitude and phase at the beat period of the two oscillations, from which the individual oscillation amplitudes and phases (and hence periods) can be determined. Phases are also determined from northern and southern polar oscillation data when available. Results indicate that the southern-period amplitude declines modestly over this interval, while the northern-period amplitude approximately doubles to become comparable with the southern-period oscillations during the equinox interval, producing clear effects in pass-to-pass oscillation properties. It is also shown that the periods of the two oscillations strongly converge over the equinox interval, such that the beat period increases significantly from $20 to more than 100 days, but that they do not coalesce or cross during the interval investigated, contrary to recent reports of the behavior of the SKR periods. Examination of polar oscillation data for similar beat phase effects yields a null result within a $10% upper limit on the relative amplitude of northern-period oscillations in the south and vice versa. This result strongly suggests a polar origin for the two oscillation periods.

We investigate magnetic data showing the presence of field-aligned magnetosphere-ionosphere coupling currents on 31 Cassini passes across Saturn's southern postmidnight auroral region. The currents are strongly modulated in magnitude, form, and position by the phase of the southern planetary period oscillations (PPOs). PPO-independent currents are separated from PPO-related currents using the antisymmetry of the latter with respect to PPO phase. PPO-independent downward currents~1.1 MA per radian of azimuth flow over the polar open field region indicative of significant plasma subcorotation are enhanced in an outer plasma sheet layer of elevated ionospheric conductivity carrying~0.8 MA rad À1and close principally in an upward directed current sheet at~17°-19°ionospheric colatitude carrying 2.3 MA rad À1 that maps to the outer hot plasma region in Saturn's magnetosphere (equatorial rangẽ 11-16 Saturn radii (R S )) colocated with the UV oval. Subsidiary downward and upward currents~0.5 MA rad À1 lie at~19°-20.5°colatitude mapping to the inner hot plasma region, but no comparable currents are detected at larger colatitudes mapping to the cool plasma regime inside~8 R S . PPO-related currents at~17.5°-20°colatitude overlap the main upward and subsidiary downward currents and carry comparable rotating upward and downward currents peaking at~1.7 MA rad À1 . The overall current layer colatitude is also modulated with 1°amplitude in the PPO cycle, maximum equatorward adjacent to the peak upward PPO current and maximum poleward adjacent to peak downward PPO current. This phasing requires the current system to be driven from the planetary atmosphere rather than directly from the magnetosphere.

One of the most striking `rags to riches' stories in the protein world is that of 14-3-3, originally identified in 1967 as merely an abundant brain protein. The first clues that 14-3-3 would play an important role in cell biology came almost 25 years later when it was found to interact with various proto-oncogene proteins and signaling proteins. The subsequent identification of 14-3-3 as a phosphoserine/phosphothreonine-binding protein firmly established its importance in cell signaling. 14-3-3 family members are found in all eukaryotes – from plants to mammals – and more than 100 binding partners have been identified to date. The targets of 14-3-3 are found in all subcellular compartments and their functional diversity is overwhelming – they include transcription factors, biosynthetic enzymes, cytoskeletal proteins, signaling molecules, apoptosis factors and tumor suppressors. 14-3-3 binding can alter the localization, stability, phosphorylation state, activity and/or molecular interactions of a target protein. Recent studies now indicate that the serine/threonine protein phosphatases PP1 and PP2A are important regulators of 14-3-3 binding interactions, and demonstrate a role for 14-3-3 in controlling the translocation of certain proteins from the cytoplasmic and endoplasmic reticulum to the plasma membrane. New reports also link 14-3-3 to several neoplastic and neurological disorders, where it might contribute to the pathogenesis and progression of these diseases.

[1] We analyze the radial distribution of electron populations inside 20 R s in Saturn's magnetosphere, and we calculate moments for these populations by a forward modeling method using composite spectra produced by the CAPS/ELS (0.6 eV to 26 keV) and the MIMI/LEMMS (15 keV to 10 MeV) instruments on board Cassini. We first calculate and harmonize both data sets in physical units and apply corrections taking into account biases introduced by spacecraft interaction with the magnetospheric environment. We then test different bimodal isotropic electron distribution models, deciding on a model with two kappa distributions. We adjust our isotropic model to the flux composite spectra with a least square method to produce three sets of fluid parameters (density, temperature, spectral index) per electron population. The radial profiles are then analyzed, revealing a relevant boundary at 9 R s in both thermal and suprathermal electron populations. Observed discontinuities in the moment profiles (sudden drop-off in cold density profile outside 9 R s , hot electrons drop-off inside 9 R s ) coincide with the known outer edge of Saturn's neutral OH cloud. Farther out, thermal electrons disappear completely beyond 15 R s while suprathermal electrons are still observed in the middle and outer magnetosphere.