Recombinant Human ALKAL2 protein

ALKAL2 (ALK and LTK ligand 2), also known as FAM150B or Augmentor-β, is a secreted protein that functions as a ligand for receptor tyrosine kinases ALK (Anaplastic Lymphoma Kinase) and LTK (Leukocyte Receptor Tyrosine Kinase). It belongs to the ALKAL family, which includes ALKAL1 (Augmentor-α), sharing structural similarities but differing in tissue expression patterns and receptor-binding affinities. ALKAL2 was identified through bioinformatic and functional studies aiming to elucidate endogenous ligands for ALK/LTK, which were previously classified as "orphan receptors" due to the lack of known activating partners.

Structurally, ALKAL2 contains conserved cysteine-rich domains critical for receptor binding and activation. It binds to the extracellular domain of ALK/LTK, triggering dimerization and autophosphorylation of the receptors, thereby activating downstream signaling pathways such as RAS/MAPK, PI3K/AKT, and JAK/STAT. These pathways regulate cell proliferation, differentiation, and survival, implicating ALKAL2 in embryonic development, tissue homeostasis, and neural function. Studies suggest its involvement in neurodevelopment, muscle regeneration, and enteric nervous system maintenance.

Recombinant ALKAL2 protein is engineered using expression systems (e.g., E. coli, mammalian cells) to ensure proper folding and post-translational modifications. Purified ALKAL2 serves as a critical tool for studying ALK/LTK signaling mechanisms, screening ALK-targeted therapies, and exploring its therapeutic potential in cancers driven by ALK aberrations (e.g., neuroblastoma, non-small cell lung cancer). Challenges in production include maintaining solubility and bioactivity, often addressed through codon optimization or fusion tags. Ongoing research focuses on clarifying its physiological roles and therapeutic applications in regenerative medicine and oncology.