Downstream of tyrosine kinase 7 (DOK7)

Downstream of tyrosine kinase 7 (DOK7), often referred to as Dok-7, is a non-catalytic cytoplasmic adaptor protein highly expressed in skeletal muscle, where it is essential for the formation and maintenance of neuromuscular synapses[1][2][3][5]. DOK7 encompasses pleckstrin homology (PH) and phosphotyrosine-binding (PTB) domains, allowing it to interact with and activate MuSK, a muscle-specific receptor tyrosine kinase critically involved in organizing and clustering acetylcholine receptors (AChRs) at the neuromuscular junction before and after birth[1][2][3][7]. Unlike most adaptor proteins, DOK7 not only acts as a substrate for MuSK but also functions uniquely as a direct activator, stabilizing MuSK phosphorylation and promoting its dimerization[2][3][7]. Genetic mutations in DOK7 cause a specific form of congenital myasthenic syndrome (CMS), typically resulting in limb-girdle muscle weakness and severe neuromuscular transmission defects, but largely sparing facial and bulbar muscles[1][5][6]. Salbutamol can be an effective therapy for DOK7-related CMS, while other drugs commonly used in CMS (e.g., acetylcholinesterase inhibitors) may be detrimental, highlighting the importance of accurate genetic diagnosis[5][6]. DOK7 is not considered an enzyme, receptor, or transporter, but rather a critical signaling adaptor with a pivotal role in neuromuscular development and disease.

Other names

Dok-7DOK7_HUMANCMS1BC4orf25downstream of tyrosine kinase 7

Modulation of MuSK activation (by stabilizing phosphorylation and promoting MuSK dimerization); Enhancement of neuromuscular transmission (for salbutamol in congenital myasthenic syndrome with DOK7 mutations)