Identification of muscle specific ring finger proteins as potential regulators of the titin kinase domain.
The giant myofibrillar protein titin contains within its C-terminal region a serine-threonine kinase of unknown function. We have identified a novel muscle specific RING finger protein, referred to as MURF-1, that binds in vitro to the titin repeats A168/A169 adjacent to the titin kinase domain. In myofibrils, MURF-1 is present within the periphery of the M-line lattice in close proximity to titin's catalytic kinase domain, within the Z-line lattice, and also in soluble form within the cytoplasm. Yeast two-hybrid screens with MURF-1 as a bait identified two other highly homologous MURF proteins, MURF-2 and MURF-3. MURF-1,2,3 proteins are encoded by distinct genes, share highly conserved N-terminal RING domains and in vitro form dimers/heterodimers by shared coiled-coil motifs. Of the MURF family, only MURF-1 interacts with titin repeats A168/A169, whereas MURF-3 has been reported to affect microtubule stability. Association of MURF-1 with M-line titin may potentially modulate titin's kinase activity similar to other known kinase-associated proteins, whereas differential expression and heterodimerization of MURF1, 2 and 3 may link together titin kinase and microtubule-dependent signal pathways in striated muscles.
European Molecular Biology Laboratory, Heidelberg, D-69117, Germany.
T
T
Centner
J
J
Yano
E
E
Kimura
A S
AS
McElhinny
K
K
Pelin
C C
CC
Witt
M L
ML
Bang
K
K
Trombitas
H
H
Granzier
C C
CC
Gregorio
H
H
Sorimachi
S
S
Labeit
D000595:Amino Acid Sequence; D000818:Animals; D064211:Connectin; D019281:Dimerization; D005455:Fluorescent Antibody Technique; D020869:Gene Expression Profiling; D006801:Humans; D051379:Mice; D016253:Microscopy, Immunoelectron; D008969:Molecular Sequence Data; D009124:Muscle Proteins / Q000737:chemistry* / Q000235:genetics* / Q000378:metabolism*; D009132:Muscles / Q000737:chemistry* / Q000166:cytology / Q000378:metabolism; D009928:Organ Specificity; D010802:Phylogeny; D020161:Physical Chromosome Mapping; D011485:Protein Binding; D011494:Protein Kinases / Q000737:chemistry* / Q000378:metabolism*; D017434:Protein Structure, Tertiary; D012333:RNA, Messenger / Q000032:analysis / Q000235:genetics; D051381:Rats; D012518:Sarcomeres / Q000737:chemistry; D016415:Sequence Alignment; D017386:Sequence Homology, Amino Acid; D020798:Two-Hybrid System Techniques; D016335:Zinc Fingers / Q000502:physiology*
D064211:Connectin; D009124:Muscle Proteins; D012333:RNA, Messenger; C413644:Rnf30 protein, mouse; C485888:TRIM54 protein, human; C577285:TTN protein, human; D011494:Protein Kinases