[SMC] From phosphorylation to phenotype - Recent key findings on kinase regulation, downstream signaling and disease sur

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[SMC] From phosphorylation to phenotype - Recent key findings on kinase regulation, downstream signaling and disease sur

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Cell Signal. 2023 Jan 3:110584. doi: 10.1016/j.cellsig.2022.110584. Online ahead of print.

ABSTRACT

Muscle-specific kinase (MuSK) is the key regulator of neuromuscular junction development. MuSK acts via several distinct pathways and is responsible for pre- and postsynaptic differentiation. MuSK is unique among receptor tyrosine kinases as activation and signaling are particularly tightly regulated. Initiation of kinase activity requires Agrin, a heparan sulphate proteoglycan derived from motor neurons, the low-density lipoprotein receptor-related protein-4 (Lrp4) and the intracellular adaptor protein Dok-7. There is a great knowledge gap between MuSK activation and downstream signaling. Recent studies using omics techniques have addressed this knowledge gap, thereby greatly contributing to a better understanding of MuSK signaling. Impaired MuSK signaling causes severe muscle weakness as described in congenital myasthenic syndromes or myasthenia gravis but the underlying pathophysiology is often unclear. This review focuses on recent advances in deciphering MuSK activation and downstream signaling. We further highlight latest break-throughs in understanding and treatment of MuSK-related disorders and discuss the role of MuSK in non-muscle tissue.

PMID:36608736 | DOI:10.1016/j.cellsig.2022.110584


Source: https://pubmed.ncbi.nlm.nih.gov/3660873 ... t6+86293ac
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