Conserved Tao Kinase Activity Regulates Dendritic Arborization, Cytoskeletal Dynamics, and Sensory Function in .

Dendritic arborization is highly regulated and requires tight control of dendritic growth, branching, cytoskeletal dynamics, and ion channel expression to ensure proper function. Abnormal dendritic development can result in altered network connectivity, which has been linked to neurodevelopmental disorders, including autism spectrum disorders (ASDs). How neuronal growth control programs tune dendritic arborization to ensure function is still not fully understood.

A Hippo-like Signaling Pathway Controls Tracheal Morphogenesis in Drosophila melanogaster.

Hippo-like pathways are ancient signaling modules first identified in yeasts. The best-defined metazoan module forms the core of the Hippo pathway, which regulates organ size and cell fate. Hippo-like kinase modules consist of a Sterile 20-like kinase, an NDR kinase, and non-catalytic protein scaffolds.

Cooperates with Oncogenic in Tumourigenesis via the JNK and PI3K Pathways in epithelial Tissue.

The oncogene (Rat Sarcoma oncogene, a small GTPase) is a key driver of human cancer, however alone it is insufficient to produce malignancy, due to the induction of cell cycle arrest or senescence. In a genetic screen for genes that cooperate with oncogenic (bearing the mutation, or ), we identified the (Sarcoma virus oncogene) family non-receptor tyrosine protein kinase genes, and , as promoting increased hyperplasia in a whole epithelial tissue context in the eye. Moreover, overexpression of cooperated with in epithelial cell clones to drive neoplastic tumourigenesis.

The Hippo Pathway Regulates Neuroblasts and Brain Size in Drosophila melanogaster.

A key question in developmental neurobiology is how neural stem cells regulate their proliferative potential and cellular diversity and thus specify the overall size of the brain. Drosophila melanogaster neural stem cells (neuroblasts) are known to regulate their ability to self-renew by asymmetric cell division and produce different types of neurons and glia through sequential expression of temporal transcription factors [1]. Here, we show that the conserved Hippo pathway, a key regulator of epithelial organ size [2-4], restricts neuroblast proliferative potential and neuronal cell number to regulate brain size.

The GTPase regulatory proteins Pix and Git control tissue growth via the Hippo pathway.

The Salvador-Warts-Hippo (Hippo) pathway is a conserved regulator of organ size and is deregulated in human cancers. In epithelial tissues, the Hippo pathway is regulated by fundamental cell biological properties, such as polarity and adhesion, and coordinates these with tissue growth. Despite its importance in disease, development, and regeneration, the complete set of proteins that regulate Hippo signaling remain undefined.

The Hippo size control pathway--ever expanding.

An important regulator of organ size and tumorigenesis is the Hippo pathway. Recent studies have unveiled increasing complexity in regulation of Hippo pathway activity at the level of the oncoprotein Yes-associated protein (YAP). The protein tyrosine phosphatase 14 (PTPN14, known as Pez in Drosophila) was identified as a protein that antagonizes the function of the key Hippo pathway protein YAP by promoting its cytoplasmic localization under high cell density conditions.

Homeodomain-interacting protein kinase regulates Hippo pathway-dependent tissue growth.

The Salvador-Warts-Hippo (SWH) pathway is an evolutionarily conserved regulator of tissue growth that is deregulated in human cancer. Upstream SWH pathway components convey signals from neighboring cells via a core kinase cassette to the transcription coactivator Yorkie (Yki). Yki controls tissue growth by modulating activity of transcription factors including Scalloped (Sd).

The sterile 20-like kinase Tao-1 controls tissue growth by regulating the Salvador-Warts-Hippo pathway.

The Salvador-Warts-Hippo (SWH) pathway is a complex signaling network that controls both developmental and regenerative tissue growth. Using a genetic screen in Drosophila melanogaster, we identified the sterile 20-like kinase, Tao-1, as an SWH pathway member. Tao-1 controls various biological phenomena, including microtubule dynamics, animal behavior, and brain development.

Eve-3: a liver enriched suppressor of Ras/MAPK signaling.

Background/aims: The developed liver is able to tightly control cellular proliferation, rapidly switching from quiescence to growth in response to specific stimuli. This suggests that growth inhibitors may be involved in the control of liver growth. We analyzed the role of the Spred-family of growth inhibitors in the liver.

Distinct requirements for the Sprouty domain for functional activity of Spred proteins.

Sprouty and Spred {Sprouty-related EVH1 [Ena/VASP (vasodilator-stimulated phosphoprotein) homology 1] domain} proteins have been identified as antagonists of growth factor signalling pathways. We show here that Spred-1 and Spred-2 appear to have distinct mechanisms whereby they induce their effects, as the Sprouty domain of Spred-1 is not required to block MAPK (mitogen-activated protein kinase) activation, while that of Spred-2 is required. Similarly, deletion of the C-terminal Sprouty domain of Spred-1 does not affect cell-cycle progression of G(0)-synchronized cells through to S-phase following growth factor stimulation, while the Sprouty domain is required for Spred-2 function.