A novel mechanism of regulation of phosphatidylinositol 3 -kinase: Tyrosine phosphorylation of p85 residue 688

Phosphatidylinositol 3-kinase (PI3K) phosphorylates membrane constituent phosphatidylinositols, producing second messengers that link membrane bound receptor signals to cellular proliferation and survival. PI3K, a heterodimer consisting of a catalytic p110 subunit and a regulatory p85 subunit, can be activated through induced association with other signaling molecules. The p85 subunit serves to both stabilize and inactivate p110. The inhibitory activity of P85 is relieved by occupancy of the N terminal SH2 domain by phosphorylated tyrosine. PI3K becomes phosphorylated and activated subsequent to a variety of stimuli. Indeed, Src family kinases have been demonstrated to phosphorylate p85 at tyrosine 688, but the role of phosphorylation in PI3K function is unclear. We decided to evaluate the importance of tyrosine phosphorylation to PI3K activity. We demonstrate that tyrosine phosphorylated p85 is associated with a higher specific activity than is non-phosphorylated PI3K. Wild type p85 inhibits PI3K enzyme activity, a process accentuated by mutation of tyrosine 688 to alanine and reversed by mutation to aspartate which functions as a phosphotyrosine mimic in multiple systems. Strikingly, the Y688D mutation completely reverses the p85 inhibitory activity on cell viability and activation of downstream protein NFkB. We demonstrate that tyrosine phosphorylated Y688 or Y688D is sufficient to bind the p85 N terminal SH2 domain, either within full length p85 or in an isolated N terminal SH2 domain, suggesting the possibility of an intramolecular interaction between phosphorylated Y688 and the p85 N terminal SH2 domain that can relieve the p85-induced inhibition of p110. Further, we provide evidence that dephosphorylation of Y688 reduces phosphorylation-induced PI3K activity. We demonstrate that tyrosine phosphatase SHP-1 can physically associate with p85 in a SH2-mediated interaction with the C terminal tail of SHP-1. This association is concomitant with both p85 dephosphorylation and decreased PI3K activity. Altogether, our data suggests the phosphorylation state of p85 is the focal point of a novel mechanism for PI3K activity regulation. As PI3K has been shown to be involved in the vital physiological processes of cell proliferation and apoptosis, a thorough understanding of the regulation of this signaling protein may provide opportunities for the design of novel treatments for cancer. ^

The prevalence of food insecurity and associated factors among households with children in Head Start programs in Houston, Texas and Birmingham, Alabama

The purposes of this study were to determine the prevalence of food insecurity and factors associated with food insecurity among households with children enrolled in Head Start programs in Houston, Texas, and Birmingham, Alabama. This cross-sectional study utilized data gathered from 688 households recruited by convenience sample from two Head Start districts in each city. Interviewers collected data from primary caregivers on demographic characteristics, dietary intake, and the six-item USDA food security module. Chi-square and logistic regression analysis were used to determine the association of food security and demographic characteristics. Comparison of means was used to analyze the association between the child's fruit and vegetable intake and the household's food security status. The prevalence of food insecurity among the sample was 34.9% (95% CI: 31.3%, 38.5%). Characteristics associated with food insecurity were the caregiver's national origin (Foreign-born (ref.) v. U.S.-born, adjusted OR = 0.36, 95% CI: 0.14, 0.94), gender of the child (male (ref.) v. female, adjusted OR = 1.44, 95% CI: 1.03, 2.01), and city of residence (Birmingham (ref.) v. Houston, adjusted OR = 0.20, 95% CI: 0.10, 0.39). Children in food insecure households consumed more daily servings of fruits and vegetables on average (mean = 2.44) than children in food secure households (mean = 2.16, p = 0.04). ^

Point-of-sale machines in school cafeterias and parental influence on child food choices

The prevalence of obesity has reached epidemic proportions in the United States. Twenty-five percent of school aged students are overweight. Schools have the opportunity to help slow this epidemic. School cafeterias in the United States feed millions of students every day through the National School Lunch Program.^ Point-of-sale machines are used in most school cafeterias to help streamline the process of purchasing school lunches. The point-of-sale software allows school personnel to place special notes on student's accounts to provide alerts about parental requests. This study investigated what the alerts are used for, who uses the alerts, and if there are any patterns by demographic characteristics. ^ Counts and percentages were used to determine what the alerts were used for and who used them. This study found that students who were white non-Hispanic, paid status, or in elementary school were most likely to have alerts placed on their accounts. Also, the majority of point-of-sale alerts were used as allowances (i.e., allowed to purchase snacks from the balance on the school lunch account), rather than restrictions (i.e., restricted from purchasing high calorie foods or specific food items). Using chi-square analysis, a total of 688 alerts were analyzed. There were significant differences in alert frequencies for intent category by grade level (p=0.000), snack access (p=0.000), and gender (p=0.002). Therefore, the results are significant, and one can conclude there is a significant relationship between gender, grade level, and snack access, and the presence of an alert on the school lunch account.^ Also, school administrators may want to take into consideration possible changes to their program, such as requiring more time to run the software. The results of this study can assist school administrators to better understand that a point-of-sale alert program may help their school lunch programs run more efficiently, while also providing parental influence on students’ food choices at the point-of-sale.^ School food service authorities should consider implementing a structured point-of-sale alert policy to encourage parental input on their children's food choices. When implementing the point-of-sale policy, schools should publicize this policy online, through school lunch menus, and parent communications increase participation throughout the school district.^