Fully one third of the proteome is processed by the secretory pathway, which has to meet the challenge of handling a large amount of cargo with high accuracy. In addition to this, the secretory pathway has to respond to alterations in the energetic/nutrition status of the environment. In order to understand the regulation of the secretory pathway, we screened a siRNA library against the human kinome and phosphatome. We found that ERK2 (but not ERK1) regulates export from the endoplasmic reticulum (ER). We show that ERK2 phosphorylates Sec16 a protein that regulates biogenesis of ER exit sites and formation of COPII vesicles. Phosphorylation of Sec16 by ERK2 regulates the dynamics of Sec16 on ER exit sites as determined by FRAP microscopy. Thus, we conclude that under nutrient-rich conditions Sec16 is highly dynamic which enables it to be more active in ER exit site biogenesis. Based on this, we expected that Sec16 is less mobile under nutrient limiting conditions. If true this would result in a higher number of Sec16 molecules per ER exit site. In fact, under nutrient-limiting conditions (serum-starvation) the number of ER exit sites is low and the Sec16 fluorescence is also lower per exit site. Importantly, starvation led to a decrease in the cellular levels of Sec16, which explains the decrease of ER exit site number under these conditions. We are currently testing whether ERK2 phosphorylation acts to protect Sec16 from degradation. Altogether, our results nicely couple the cellular energetic homeostasis to secretion. Under anabolic conditions, ERK2 signals to Sec16, which primes ER exit sites for a higher secretory load. Under nutrient-limiting conditions, Sec16 is degraded, thereby limiting the number of ER exit sites. Thus, Sec16 is a platform for integrating and decoding the nutritional load that cell are exposed to.