Lipid-mediated membrane binding properties of Disabled-2.

Disabled-2 (Dab2) is an adaptor protein involved in several biological processes ranging from endocytosis to platelet aggregation. During endocytosis, the Dab2 phosphotyrosine-binding (PTB) domain mediates protein binding to phosphatidylinositol 4,5-bisphosphate (PtdIns(4,5)P(2)) at the inner leaflet of the plasma membrane. As a result of platelet activation, Dab2 is released from α-granules and associates with both the αIIbβ3 integrin receptor and sulfatide lipids on the platelet surface through its N-terminal region including the PTB domain (N-PTB), thus, modulating platelet aggregation.

Disabled-2 modulates homotypic and heterotypic platelet interactions by binding to sulfatides.

Disabled-2 (Dab2) inhibits platelet aggregation by competing with fibrinogen for binding to the α(IIb) β(3) integrin receptor, an interaction that is modulated by Dab2 binding to sulfatides at the outer leaflet of the platelet plasma membrane. The disaggregatory function of Dab2 has been mapped to its N-terminus phosphotyrosine-binding (N-PTB) domain. Our data show that the surface levels of P-selectin, a platelet transmembrane protein known to bind sulfatides and promote cell-cell interactions, are reduced by Dab2 N-PTB, an event that is reversed in the presence of a mutant form of the protein that is deficient in sulfatide but not in integrin binding.

Shorter exposures to harder X-rays trigger early apoptotic events in Xenopus laevis embryos.

Background: A long-standing conventional view of radiation-induced apoptosis is that increased exposure results in augmented apoptosis in a biological system, with a threshold below which radiation doses do not cause any significant increase in cell death. The consequences of this belief impact the extent to which malignant diseases and non-malignant conditions are therapeutically treated and how radiation is used in combination with other therapies. Our research challenges the current dogma of dose-dependent induction of apoptosis and establishes a new parallel paradigm to the photoelectric effect in biological systems.

Sulfatides partition disabled-2 in response to platelet activation.

Background: Platelets contact each other at the site of vascular injury to stop bleeding. One negative regulator of platelet aggregation is Disabled-2 (Dab2), which is released to the extracellular surface upon platelet activation. Dab2 inhibits platelet aggregation through its phosphotyrosine-binding (PTB) domain by competing with fibrinogen for alphaIIbbeta3 integrin receptor binding by an unknown mechanism.

A novel heme-regulatory motif mediates heme-dependent degradation of the circadian factor period 2.

Although efforts have been made to identify circadian-controlled genes regulating cell cycle progression and cell death, little is known about the metabolic signals modulating circadian regulation of gene expression. We identify heme, an iron-containing prosthetic group, as a regulatory ligand controlling human Period-2 (hPer2) stability. Furthermore, we define a novel heme-regulatory motif within the C terminus of hPer2 (SC(841)PA) as necessary for heme binding and protein destabilization.