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Activin A receptor type 1B (ALK4)
- Target
- ALK4
- Molecular classification
- Receptor, Type I receptor serine/threonine kinase, Growth/differentiation factor receptor
01
Overview
Activin A receptor type 1B (ALK4) is a cell surface serine/threonine kinase that acts as a critical signaling receptor for activin and related ligands in the TGF-β (transforming growth factor beta) superfamily. It forms a receptor complex with type II activin receptors (ACVR2A or ACVR2B) upon ligand binding, leading to phosphorylation and activation of SMAD2 and SMAD3 transcription factors, which regulate diverse cellular processes including cell growth, differentiation, apoptosis, and immune modulation. ALK4 plays an essential role in development, neurobiology, reproductive health, and tissue repair, and its dysregulation has been implicated in cancer, fibrosis, and inflammatory diseases.
- Other names
- Activin receptor type-1BActivin receptor-like kinase 4ACVR1BActRIBActR-IBACVRLK4Serine/threonine-protein kinase receptor R2SKR2
02
Mechanism of action
Inhibition of serine/threonine kinase signaling (blockade of activin/ALK4 pathway); Ligand sequestration (neutralizing ligand before receptor activation); Disruption of SMAD2/3 phosphorylation/transcription
03
Biological functions
Signal transductionCell proliferationDiferentiationTranscription regulationApoptosisImmune responseNeuronal development and survivalWound healingRegulation of follicle development
04
Disease associations
CancerInfertility (reproductive disorders)FibrosisInflammationNeuronal diseasesOther (e.g., wound healing, tissue repair)
05
Safety considerations
Off-target effects on TGF-β pathways (broad physiological roles)Potential impact on fertility, embryonic development, or wound healing (due to pathway inhibition)Immunosuppression or impaired tissue repair (therapeutic blockade risks)
06
Interacting drugs
There are no major small-molecule drugs or biologics in standard clinical use that specifically target ALK4/ACVR1B; however, small-molecule kinase inhibitors, decoy receptors, and antibodies targeting the activin signaling pathway are in development and may include experimental molecules aimed at TGF-β family serine/threonine kinase receptors
07
Biomarkers
SMAD2/SMAD3 phosphorylation status (downstream pathway activation)Expression of activin A or ACVR1B in tumors or reproductive tissue (context-dependent)
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