Preferred Label : ALK Pathway;
NCIt related terms : ALK in cardiac myocytes;
Alternative definition : BIOCARTA: Heart formation is cued by a combination of positive and negative signals
from surrounding tissues. Inhibitory signals that block heart formation in anterior
paraxial mesoderm include Wnt family members expressed in dorsal neural tube and anti-BMPs
expressed in the axial tissues (i.e., noggin in the notochord). Wnt signaling pathway,
which is essential for setting up the entire body pattern during embryonic development,
involves glycogen synthase kinase-3 (GSK3). In the absence of Wnt signaling, GSK3
is active and phosphorylates b-catenin resulting in its degradation by ubiquitin-mediated
proteolysis. Activation of Wnt signaling inhibits GSK3, thereby preventing phosphorylation
of b-catenin, which is then able to move to the nucleus. There it associates with
members of the LEF-1/TCF family of transcription factors, which activate the transcription
of genes like cyclin-D1, myc, and MMPs. The Wnt signaling pathway is blocked by a
family of secreted proteins such as crescent and Dkk-1 sufficient for induction of
heart formation in posterior mesoderm. BMP signaling can also be blocked by the BMP
antagonists noggin and chordin, which are secreted from the notochord and cooperate
with Wnts to prevent cardiogenesis. Receptors for BMPs, members of the transforming
growth factor-beta (TGFb) superfamily, are persistently expressed during cardiac development,
yet mice lacking type II or type IA BMP receptors die at gastrulation and cannot be
used to assess potential later roles in creation of the heart. Activin receptor-like
kinase 3 (ALK3) is specifically required at mid-gestation for normal development of
the trabeculae, compact myocardium, interventricular septum, and endocardial cushion.
Cardiac muscle lacking ALK3 is specifically deficient in expressing TGFb2, an established
paracrine mediator of cushion morphogenesis. In humans, congenital heart defects occur
with a prevalence of at least 1% in newborns, and are even more common in death before
term. Most frequent are defects in septation and the cardiac valves, and few single
gene etiologies are known. The invariable defects in myocardium and AV cushion resulting
from congenital deletion of ALK3 provide strong support for its assessment as a candidate
gene in human congenital heart disease. (This definition may be outdated - see the
DesignNote.);
NCIt note : The BIOCARTA Definition (ALT_DEFINITION) for this pathway concept was provided by
BioCarta. This property was not created by, nor is it maintained by the NCI Thesaurus
staff. Additionally, BioCarta is no longer updating its pathway data; thus, the BIOCARTA
Definition might be outdated or inaccurate. Please see the Terms and Conditions for
Use at http://www.biocarta.com/.;
Biocarta ID : h_alkPathway;
Origin ID : C38982;
UMLS CUI : C1515846;
Semantic type(s)
- has_gene_product_element
- pathway_has_gene_element
