Non-immune hydrops fetalis is associated with bi-allelic pathogenic variants in the MYB Binding Protein 1a (MYBBP1A) gene.

Non-immune hydrops fetalis (NIHF) is a rare entity characterized by excessive accumulation of fluid within the fetal extravascular compartments and body cavities. Here we present two intrauterine fetal demises with NIHF presenting with oligohydramnios, cystic hygroma, pleural effusion, and generalized hydrops with predominance of subcutaneous edema. The fetuses also presented with ascites, severe and precocious IUGR and skeletal anomalies.

Myosin Vb as a tumor suppressor gene in intestinal cancer.

Colorectal cancer causes >900,000 deaths every year and a deeper understanding of the molecular mechanisms underlying this disease will contribute to improve its clinical management and survival. Myosin Vb (MYO5B) regulates intracellular vesicle trafficking, and inactivation of this myosin disrupts the polarization and differentiation of intestinal epithelial cells causing microvillous inclusion disease (MVID), a rare congenital disorder characterized by intractable life-threatening diarrhea. Here, we show that the loss Myosin Vb interfered with the differentiation/polarization of colorectal cancer cells.

The role of the calmodulin-binding and calmodulin-like domains of the epidermal growth factor receptor in tyrosine kinase activation.

The epidermal growth factor receptor (EGFR) harbors a calmodulin (CaM)-binding domain (CaM-BD) and a CaM-like domain (CaM-LD) upstream and downstream, respectively, of the tyrosine kinase (TK) domain. We demonstrate in this paper that deletion of the positively charged CaM-BD (EGFR/CaM-BD∆) inactivated the TK activity of the receptor. Moreover, deletion of the negatively charged CaM-LD (EGFR/CaM-LD∆), leaving a single negative residue (glutamate), reduced the activity of the receptor.

Ca signaling and Src-kinases-controlled cellular functions.

Calcium-mediated signaling and the functionality of Src-family tyrosine kinases (SFKs) are two interconnected processes. Activation of these kinases, which are coupled to a series of receptors, mediates Ca mobilization by regulating Ca channels, and the generated Ca signal in turn exerts control on the kinase activity via calmodulin. In this review, we shall cover the regulation of selected processes where crosstalk between the functionality of SFKs and the Ca signal occurs during the lifespan of the cell, when subjected to different extracellular or intracellular stimuli.

Src-family tyrosine kinases and the Ca signal.

In this review, we shall describe the rich crosstalk between non-receptor Src-family kinases (SFKs) and the Ca transient generated in activated cells by a variety of extracellular and intracellular stimuli, resulting in diverse signaling events. The exchange of information between SFKs and Ca is reciprocal, as it flows in both directions. These kinases are main actors in pathways leading to the generation of the Ca signal, and reciprocally, the Ca signal modulates SFKs activity and functions.

The activating role of phospho-(Tyr)-calmodulin on the epidermal growth factor receptor.

The activity of calmodulin (CaM) is modulated not only by oscillations in the cytosolic concentration of free Ca(2+), but also by its phosphorylation status. In the present study, the role of tyrosine-phosphorylated CaM [P-(Tyr)-CaM] on the regulation of the epidermal growth factor receptor (EGFR) has been examined using in vitro assay systems. We show that phosphorylation of CaM by rat liver solubilized EGFR leads to a dramatic increase in the subsequent phosphorylation of poly-L-(Glu:Tyr) (PGT) by the receptor in the presence of ligand, both in the absence and in the presence of Ca(2+).

Ca2+/Calmodulin and Apo-Calmodulin Both Bind to and Enhance the Tyrosine Kinase Activity of c-Src.

Src family non-receptor tyrosine kinases play a prominent role in multiple cellular processes, including: cell proliferation, differentiation, cell survival, stress response, and cell adhesion and migration, among others. And when deregulated by mutations, overexpression, and/or the arrival of faulty incoming signals, its hyperactivity contributes to the development of hematological and solid tumors. c-Src is a prototypical member of this family of kinases, which is highly regulated by a set of phosphorylation events.