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We explore the spatial and temporal variations in denudation rates in the northern Pamir—Tian Shan region using 10Be‐derived denudation rates from modern (n = 110) and buried sediment (2.0–2.7 Ma; n = 3), and long‐term exhumation rates from published apatite fission track (AFT; n = 705) and apatite (U‐Th‐Sm)/He (AHe; n = 211) thermochronology. We found moderate correlations between denudation rates and topographic metrics and weak correlations between denudation rates and annual rainfall, highlighting complex linkages among tectonics, climate, and surface processes that vary locally. The 10Be data show a spatial trend of decreasing modern denudation rates from west to east, suggesting that deformation and precipitation control denudation in the northern Pamir and western Tian Shan. Farther east, the denudational response of the landscape to Quaternary glaciations is more pronounced and reflected in our data. Modern 10Be denudation rates are generally higher than the long‐term AFT and AHe exhumation rates across the studied area. In the Kyrgyz Tian Shan, on average, the highest 10Be denudation rates are recorded in the Terskey range, south of Lake Issyk‐Kul. Here, modern denudation rates are higher than 10Be‐derived paleo‐denudation rates, which are comparable in magnitude with the long‐term exhumation rates inferred from AFT and AHe. We propose that denudation in the region, particularly in the Terskey range, remained relatively steady during the Neogene and early Pleistocene. Denudation increased due to glacial‐interglacial cycles in the Quaternary, but this occurred after the onset and intensification of the Northern Hemisphere glaciations at 2.7 Ma. Plain Language Summary: Tectonic forces create mountains, while climatically modulated erosion breaks them down into sediment that rivers carry to the final depositional basin. This cycle affects global climate over long periods, but it's unclear whether mountain uplift causes climate change or if climate cooling leads to faster erosion and mountain uplift. To tackle these questions, we explore temporal and spatial changes in rates of denudation in the northern Pamir—Tian Shan region and find that rates remained steady during the Neogene and early Pleistocene but increased due to glacial‐interglacial cycles in the Quaternary. We also find that modern denudation rates decrease from west to east. This suggests that tectonic deformation controls denudation in the northern Pamir and western Tian Shan, while further east the denudational response of the landscape to Quaternary glaciations is more pronounced and reflected in our data. Dominant controls on modern denudation rates vary across the mountain range and reflect local factors. Our results highlight how the evolution of mountain belts strongly depends on denudation, which reflects complex interactions between tectonics, climatic changes, and surface processes, and show how in the northern Pamir—Tian Shan region, climate cooling during the Quaternary period resulted in faster erosion rates. Key Points: Modern denudation rates are higher than paleo‐denudation rates from 2.0 to 2.7 Ma and exhumation rates inferred from thermochronologyDenudation in the Terskey range remained steady during the Neogene and early Pleistocene and then increased in the Quaternary after 2.0 MaThe denudational response to Quaternary glaciations is detectable in the Kyrgyz and Chinese portions of the Tian Shan [ABSTRACT FROM AUTHOR]

We use cosmogenic 10Be and 26Al in both bedrock and fluvial sediments to investigate controls on erosion rates and sediment supply to river basins at the regional scale in the Kimberley, NW Australia. The area is characterised by lithologically controlled morphologies such as cuestas, isolated mesas and extensive plateaus made of slightly dipping, extensively jointed sandstones. All sampled bedrock surfaces at plateau tops, ridgelines, and in the broader floodplain of major rivers over the region show similar slow lowering rates between 0.17 and 4.88 m.Myr‐1, with a mean value of 1.0 ± 0.6 m.Myr‐1 (n=15), whilst two bedrock samples collected directly within river‐beds record rates that are one to two orders of magnitude higher (14.4 ± 1.5 and 20.9 ± 2.5 m.Myr‐1, respectively). Bedrock 26Al/10Be ratios are all compatible with simple, continuous sub‐aerial exposure histories. Modern river sediment yield lower 10Be and 26Al concentrations, apparent 10Be basin‐wide denudation rates ranging between 1.8 and 7.7 m.Myr‐1, with a median value of 2.6 m.Myr‐1, more than double the magnitude of bedrock erosion rates. 26Al/10Be ratios of the sediment samples are lower than those obtained for bedrock samples. We propose that these depleted 26Al/10Be ratios can largely be explained by the supply of sediment to river basins from the slab fragmentation and chemical weathering of channel gorge walls and plateau escarpments that result in diluting the cosmogenic nuclide concentration in river sediments measured at the basin outlets. The results of a mass‐balance model suggest that ~60–90% of river sediment in the Kimberley results from the breakdown and chemical weathering of retreating vertical sandstone rock‐walls in contrast to sediment generated by bedrock weathering and erosion on the plateau tops. This study emphasises the value of analysing two or more isotopes in basin‐scale studies using cosmogenic nuclides, especially in slowly eroding post‐orogenic settings. © 2019 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

In accordance with our recent results obtained with cultured rat hepatocytes [Fujioka, T. & Ui, M. (2001) Eur. J. Biochem. 268, 25–34], epidermal growth factor (EGF) gave rise to transient tyrosine phosphorylation of insulin receptor substrates (IRS-1 and IRS-2), thereby activating the bound phosphatidylinositol 3-kinase in human epidermoid carcinoma A431 cells normally abundant in EGF receptors (EGFR) and Chinese hamster ovary (CHO) cells transfected with full-length EGFR. These actions of EGF, although much smaller in magnitude than those of insulin or IGF-I in the same cells, were accompanied by tyrosine phosphorylation of EGFR rather than insulin or IGF-I receptors, never observed in wild-type CHO cells expressing no EGFR, and totally inhibited by an inhibitor of EGFR kinase, AG1478, that was without effect on insulin or IGF-I actions. Recombinant IRS-1 was phosphorylated on tyrosines upon incubation with purified EGFR from A431 cells and 32P-labeled ATP. When CHO cells were transfected with C-terminal truncated EGFR lacking three NPXY motifs responsible for direct binding to phosphotyrosine-binding domains of IRSs, no effect of EGF could be observed. We suggest that tyrosine phosphorylation of IRS-1 or IRS-2 could mediate EGFR-induced activation of phosphatidylinositol 3-kinase in mammalian cells. [ABSTRACT FROM AUTHOR]

Examines the involvement of insulin receptor substrates in epidermal growth factor induced activation of phosphatidylinositol 3-kinase. Development of tyrosine phosphorylation of insulin receptor substrate; Display of receptor desensitization; Mediation of the epidermal growth factor receptor.

Examines the decrease in cAMP phosphodiesterase activity in hepatocytes cultured with herbimycin A. Relation of polymerization to inhibition of tyrosine phosphorylation of α-tubulin; Incubation of rat hepatocyte with glucagon with herbimycin A; Effects of herbimycin.