Pediatric Osteomyelitis: A Case Report.

Many health care facilities are exposed to parents seeking medical attention because of their child limping. It can be challenging for providers to determine the diagnosis of a limping child due to other conditions presenting with similar symptomology, but it is important to differentiate between the multitude of diagnoses based on associated symptoms, diagnostic tests, and the child's physical examination and age. Most limping is caused by a mild, self-limiting event, although it can be sign of a serious or life-threatening condition. This case presentation describes a toddler who presented to the emergency department with a limp and increasing pain.

AFAP1L1 is a novel adaptor protein of the AFAP family that interacts with cortactin and localizes to invadosomes.

The actin-filament associated protein (AFAP) family of adaptor proteins consists of three members: AFAP1, AFAP1L1, and AFAP1L2/XB130 with AFAP1 being the best described as a cSrc binding partner and actin cross-linking protein. A homology search of AFAP1 recently identified AFAP1L1 which has a similar sequence, domain structure and cellular localization; however, based upon sequence variations, AFAP1L1 is hypothesized to have unique functions that are distinct from AFAP1. While AFAP1 has the ability to bind to the SH3 domain of the nonreceptor tyrosine kinase cSrc via an N-terminal SH3 binding motif, it was unable to bind cortactin. However, the SH3 binding motif of AFAP1L1 was more efficient at interacting with the SH3 domain of cortactin and not cSrc. AFAP1L1 was shown by fluorescence microscopy to decorate actin filaments and move to punctate actin structures and colocalize with cortactin, consistent with localization to invadosomes. Upon overexpression in A7r5 cells, AFAP1L1 had the ability to induce podosome formation and move to podosomes without stimulation. Immunohistochemical analysis of AFAP1L1 in human tissues shows differential expression when contrasted with AFAP1 with localization of AFAP1L1 to unique sites in muscle and the dentate nucleus of the brain where AFAP1 was not detectable. We hypothesize AFAP1L1 may play a similar role to AFAP1 in affecting changes in actin filaments and bridging interactions with binding partners, but we hypothesize that AFAP1L1 may forge unique protein interactions in which AFAP1 is less efficient, and these interactions may allow AFAP1L1 to affect invadosome formation.

A Polymorphic Variant of AFAP-110 Enhances cSrc Activity.

Enhanced expression and activity of cSrc are associated with ovarian cancer progression. Generally, cSrc does not contain activating mutations; rather, its activity is increased in response to signals that affect a conformational change that releases its autoinhibition. In this report, we analyzed ovarian cancer tissues for the expression of a cSrc-activating protein, AFAP-110. AFAP-110 activates cSrc through a direct interaction that releases it from its autoinhibited conformation. Immunohistochemical analysis revealed a concomitant increase of AFAP-110 and cSrc in ovarian cancer tissues. An analysis of the AFAP-110 coding sequence revealed the presence of a nonsynonymous, single-nucleotide polymorphism that resulted in a change of Ser403 to Cys403. In cells that express enhanced levels of cSrc, AFAP-110(403C) directed the activation of cSrc and the formation of podosomes independently of input signals, in contrast to wild-type AFAP-110. We therefore propose that, under conditions of cSrc overexpression, the polymorphic variant of AFAP-110 promotes cSrc activation. Further, these data indicate amechanismby which an inherited genetic variation could influence ovarian cancer progression and could be used to predict the response to targeted therapy.