RESUMO
The Drosophila nonreceptor protein tyrosine phosphatase, Corkscrew (Csw), functions positively in multiple receptor tyrosine kinase (RTK) pathways, including signaling by the epidermal growth factor receptor (EGFR). Detailed phenotypic analyses of csw mutations have revealed that Csw activity is required in many of the same developmental processes that require EGFR function. However, it is still unclear where in the signaling hierarchy Csw functions relative to other proteins whose activities are also required downstream of the receptor. To address this issue, genetic interaction experiments were performed to place csw gene activity relative to the EGFR, spitz (spi), rhomboid (rho), daughter of sevenless (DOS), kinase-suppressor of ras (ksr), ras1, D-raf, pointed (pnt), and moleskin. We followed the EGFR-dependent formation of VA2 muscle precursor cells as a sensitive assay for these genetic interaction studies. First, we established that Csw has a positive function during mesoderm development. Second, we found that tissue-specific expression of a gain-of-function csw construct rescues loss-of-function mutations in other positive signaling genes upstream of rolled (rl)/MAPK in the EGFR pathway. Third, we were able to infer levels of EGFR signaling in various mutant backgrounds during myogenesis. This work extends previous studies of Csw during Torso and Sevenless RTK signaling to include an in-depth analysis of the role of Csw in the EGFR signaling pathway.
Assuntos
Proteínas de Drosophila , Drosophila/genética , Receptores ErbB/metabolismo , Proteínas Tirosina Fosfatases/metabolismo , Transdução de Sinais , Proteínas ras , Animais , Animais Geneticamente Modificados , Cruzamentos Genéticos , Drosophila/fisiologia , Proteínas de Ligação ao GTP/genética , Imuno-Histoquímica , Mesoderma/metabolismo , Modelos Biológicos , Músculos/metabolismo , Mutação , Fenótipo , Proteínas Quinases/genética , Proteínas Tirosina Fosfatases/genética , Proteínas Tirosina Fosfatases não Receptoras , Proteínas Proto-Oncogênicas pp60(c-src)/genética , Distribuição TecidualRESUMO
Traditionally, anterior cruciate ligament (ACL) injuries have been difficult to diagnose in the Casualty Department. Studies have shown that the anterior drawer test has a poor sensitivity both in acute and chronic ACL deficient knees [4, 6, 9]; thus, more emphasis has been placed on the pivot shift and Lachman tests [3]. We report four cases of proven ACL rupture where clinical examination revealed an absent pivot shift and a near normal Lachman test following a displaced bucket handle tear of the medial meniscus. This finding has been reproduced in cadaver studies, and we conclude that if the history strongly suggests an ACL injury and examination reveals a stable knee, then the dual pathology of medial meniscus tear and ACL rupture should be suspected.