What does this research mean for the field?

The titin kinase domain acts as a mechanical sensor that controls muscle gene expression and protein turnover via a signaling complex involving nbr1, p62, and MuRF2, and disruption of this pathway causes hereditary muscle disease. Novelty: ClaimNovelty.NOVEL_FINDING. Consensus alignment: ConsensusAlignment.NEUTRAL.

What question did this study set out to answer?

To elucidate the mechanosensory signaling pathway linked to the kinase domain of titin and its role in muscle gene expression, protein turnover, and hereditary disease.

March 31, 2005Science

The Kinase Domain of Titin Controls Muscle Gene Expression and Protein Turnover

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Authors

SLStephan LangeGeneral Cardiology FXFengqing XiangKarolinska Institutet AYAndrey R YakovenkoR-Pharm (Russia)

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Implication

Defines TK-nbr1-p62-MuRF2-SRF mechanosignaling; leaves open its role in cardiac adaptation or disease.

Key Points

To elucidate the mechanosensory signaling pathway linked to the kinase domain of titin and its role in muscle gene expression, protein turnover, and hereditary disease.
Investigated molecular interactions involving the titin kinase domain, the zinc-finger protein nbr1, p62/SQSTM1, and the E3 ubiquitin ligase MuRF2.
Examined the effects of mechanical inactivity on MuRF2 nuclear translocation and serum response transcription factor (SRF) activity.
Analyzed the pathological impact of a human titin kinase mutation on the identified signaling complex.
The titin kinase domain associates with nbr1 via a mechanically inducible conformation to target p62/SQSTM1 and MuRF2 to sarcomeres.
Mechanical inactivity induces nuclear translocation of MuRF2, which reduces nuclear SRF levels and represses muscle gene transcription.
A human mutation within the titin kinase domain disrupts this mechanosensitive pathway, leading to hereditary muscle disease.

Cite This Study

Lange et al. (2005) studied this question.

synapsesocial.com/papers/6a19b00fa2165c1276dee773 https://doi.org/10.1126/science.1110463

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The Kinase Domain of Titin Controls Muscle Gene Expression and Protein Turnover

Discussion

Member takes

Implication

Key Points

Cite This Study

The Kinase Domain of Titin Controls Muscle Gene Expression and Protein Turnover

Discussion

Member takes

Implication

Key Points

Cite This Study

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