The purpose of this study was to examine the validity of a 20-m shuttle-run test as an aerobic fitness test for Japanese children, adolescents, and young adults. Participants were 62 boys and 70 girls aged 8–17 years and 56 men and 99 women aged 18–23 years. Stepwise regression analysis was used to elucidate the relationship between shuttle-run performance, age, gender, and anthropometric parameters (as independent variables) and peak oxygen uptake (VO2peak), determined directly on a treadmill, as a dependent variable. We observed high multiple correlations for adults (R2 = .88) and for children and adolescents (R2 = .80). Therefore, it is suggested that our multiple regression equations are more appropriate for predicting VO2peak in Japanese children, adolescents, and adults.

Latent membrane protein 2A (LMP2A) is expressed in latent Epstein-Barr virus (EBV) infection. LMP2A functions to downregulate B-cell signal transduction and viral reactivation from latency in EBV-immortalized B cells in vitro, and acts to provide B cells with both a survival and developmental signal in vivo. Identification of proteins associated with LMP2A is important for elucidation of the mechanism that LMP2A employs to regulate B-cell signal transduction and EBV latency. LMP2A is constitutively tyrosine phosphorylated and is associated with protein tyrosine kinases such as Lyn and Syk when specific LMP2A tyrosines are phosphorylated. The amino-terminal domain of LMP2A includes multiple proline-rich regions, which may provide binding sites for proteins containing SH3 or WW domains. In this study, we demonstrate that four cellular proteins bind specifically to two PPPPY (PY) motifs present within the LMP2A amino-terminal domain. Protein microsequence analysis determined that three of these proteins were AIP4, WWP2/AIP2, and Nedd4. All of these proteins are members of the Nedd4-like ubiquitin-protein ligases family and have conserved domains including the C2, WW, and ubiquitin-protein ligase domain. The mutation of both PY motifs completely abolished binding activity of these proteins to LMP2A and the interaction of AIP4 and WWP2 with LMP2A was confirmed in cell lines expressing LMP2A, WWP2, and AIP4. Furthermore, a reduction in the level of Lyn and the rapid turnover of LMP2A and Lyn were observed in LMP2A-expressing cells. These findings suggest that LMP2A recruits Nedd4-like ubiquitin-protein ligases and B-cell signal transduction molecules, resulting in the degradation of LMP2A and Lyn by a ubiquitin-dependent mechanism. This provides a new means by which LMP2A may modulate B-cell signal transduction.

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Epstein-Barr virus (EBV) infects primary human B lymphocytes in culture, creating immortalized lymphoblastoid cell lines (LCLs) (for reviews, see references 14 and 15). In EBVimmortalized LCLs, the EBV genome expresses a restricted set of nine viral proteins, two small viral RNAs, and the BamHI A rightward transcripts (for reviews, see references 14 and 15). Six of these latently expressed proteins are EpsteinBarr nuclear antigens (EBNA1, EBNA2, EBNA3A, EBNA3B, EBNA3C, and EBNA-LP), and three are latent membrane proteins (latent membrane protein 1 [LMP1], LMP2A, and LMP2B). EBV can be detected in a subset of nonproliferating memory B cells from EBV-infected healthy individuals (for a review, see reference 25). Studies from these latently infected B cells indicate that LMP2A may be the most readily detected latent mRNA of any of the EBV proteins associated with EBV latent infections (for a review, see reference 25). In addition, LMP2A expression is detected in many of the proliferative disorders associated with EBV infection (for reviews, see references 14, 15, and 25).LMP2A is a 497-amino-acid type II membrane protein with 12 transmembrane domains (16,22). The cytoplasmic aminoterminal tail of LMP2A contains phosphorylated tyrosine residues and proline-rich regions that are critical for the ability of LMP2A to interact with a variety of cellular proteins containing specific interactive modular domains, such as SH2 and WW domains. The Src family Lyn protein tyrosine kinase (PTK) binds to tyrosine 112. The Syk PTK binds to the LMP2A immunoreceptor tyrosine-based activation motif (ITAM) at tyrosine 74 and 85 via SH2-phosphotyrosine interactions (7, 8). LMP2A blocks B-cell receptor (BCR)-mediated signal transduction in EBV-immortalized LCLs. These observations have led to a model in which LMP2A maintains viral latency by blocking normal cellular signaling. The association of LMP2A with Src family and Syk PTKs is essential for this activity.Transgenic mice expressing LMP2A downstream of the immunoglobulin (Ig) -heavy-chain enhancer and promoter (E) have highlighted the ability of LMP2A to impart developmental and survival signals to developing B cells despite blocking BCR signal transduction in vitro (1, 2). Normally, B cells lacking a cognate BCR have been shown to rapidly undergo apoptosis (10). In LMP2A transgenic mice, however, LMP2A causes a developmental alteration where the requirement for BCR expression is bypassed, resulting in BCR-negative B cells (1, 2). This ability of LMP2A to drive B-cell development and survival in the absence of normal BCR signals is most dramatically observed when LMP2A transgenic mice are bred with mice with the recombinase-activating gene 1-deficient (RAG-1 Ϫ/Ϫ ) background. In this background, LMP2A drives B-cell development, resulting in B cells that are capable of exiting the bone marrow and persisting in the periphery (1, 2). These results suggest that LMP2A may promote B-cell survival or provide a specific signal that allows EBV to gain access to a particular B-cell compartmen...