PEAK3/C19orf35 pseudokinase, a new NFK3 kinase family member, inhibits CrkII through dimerization.

Members of the New Kinase Family 3 (NKF3), PEAK1/SgK269 and Pragmin/SgK223 pseudokinases, have emerged as important regulators of cell motility and cancer progression. Here, we demonstrate that C19orf35 (PEAK3), a newly identified member of the NKF3 family, is a kinase-like protein evolutionarily conserved across mammals and birds and a regulator of cell motility. In contrast to its family members, which promote cell elongation when overexpressed in cells, PEAK3 overexpression does not have an elongating effect on cell shape but instead is associated with loss of actin filaments. Through an unbiased search for PEAK3 binding partners, we identified several regulators of cell motility, including the adaptor protein CrkII. We show that by binding to CrkII, PEAK3 prevents the formation of CrkII-dependent membrane ruffling. This function of PEAK3 is reliant upon its dimerization, which is mediated through a split helical dimerization domain conserved among all NKF3 family members. Disruption of the conserved DFG motif in the PEAK3 pseudokinase domain also interferes with its ability to dimerize and subsequently bind CrkII, suggesting that the conformation of the pseudokinase domain might play an important role in PEAK3 signaling. Hence, our data identify PEAK3 as an NKF3 family member with a unique role in cell motility driven by dimerization of its pseudokinase domain.

Mechanisms underlying plant sexual dimorphism in multi-trophic arthropod communities.

A growing body of research documents the importance of plant genetic effects on arthropod community structure. However, the mechanisms underlying these effects are often unclear. Additionally, plant genetic effects have largely been quantified in common gardens, thus inflating the estimates of their importance by minimizing levels of natural variation. Using Valeriana edulis, a dioecious plant with genetically based sex determination, we conducted surveys and experiments on wild-grown individuals to document field patterns of arthropod association between the sexes and the mechanisms underlying these plant genetic effects. Three years of surveys revealed strong and consistent sex-biased arthropod association in wild-grown plants: female plants supported 4-fold, 1.5-fold, and 4-fold higher densities of aphids, aphid predators, and aphid-tending ants, respectively, compared to males. There was mixed evidence that the female bias for aphids was due to higher plant quality, while we found no difference between plant sexes in aphid preference or the top-down effects of predators and tending ants. Female bias for ants was due to both the greater attractiveness of female plants (direct effect mediated by floral nectar) and an independent, weaker effect of higher aphid abundance on females (density-mediated indirect effect). Conversely, the female bias for predators was driven solely by the greater attractiveness of female plants. We did not find interaction modification, i.e., ant-aphid and predator-aphid interactions were equivalent between plant sexes. Plant sex explained 0.24%, 2.28%, and 4.42% of the variance in aphids, predators, and ants, respectively, values comparable to but slightly weaker than those previously reported from common-garden studies. In contrast to the prediction of diminished plant genetic effects with increasing trophic level, we show how weak indirect effects on predators and parasitoids (via herbivores) can be complemented by strong direct effects via common plant traits (floral resources). In summary, we document direct and indirect effects of genetically based sex on a multi-trophic arthropod community that were expressed in wild-grown plants across multiple years.