Abstract
The magnitude of agonist-induced Ca2+ sensitization of force is tissue-dependent, but an explanation for this diversity is unknown. Ca2+ sensitization is thought to involve a G-protein-mediated inhibition of myosin light chain phosphatase activity by phosphorylation of the myosin-targeting subunit (MYPT). The MYPT has two isoforms that differ by a central insert, which lies near this phosphorylation site. Expression of MYPT isoforms is both developmentally regulated and tissue-specific. We hypothesized that the presence or absence of the central insert determines the magnitude of agonist-induced Ca2+ sensitization. Throughout development, the chicken aorta exclusively expresses the splice-in MYPT isoform, and guanosine 5′-O-(thiotriphosphate) (GTPγS) produces a significant force enhancement. Early during development, the chicken gizzard expresses the splice-in MYPT isoform, and GTPγS produced a Ca2+ sensitization. In the gizzard coincident with the shift in expression from the splice-in to splice-out MYPT isoform, GTPγS no longer produced force enhancement. In addition, adenosine 5′-O-(thiotriphosphate) (ATPγS) phosphorylated only adult gizzard tissue, the only tissue that did not demonstrate a Ca2+ sensitization. These results suggest that the relative expression of splice-in/splice-out MYPT isoforms determines the magnitude of agonist-induced force enhancement and that MYPT phosphorylation is not required for Ca2+ sensitization.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 4422-4427 |
| Number of pages | 6 |
| Journal | Journal of Biological Chemistry |
| Volume | 277 |
| Issue number | 6 |
| DOIs | |
| State | Published - Feb 8 2002 |
| Externally published | Yes |
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ASJC Scopus subject areas
- Biochemistry
Cite this
Agonist-induced force enhancement : The role of isoforms and phosphorylation of the myosin-targeting subunit of myosin light chain phosphatase. / Richards, Christopher T.; Ogut, Ozgur; Brozovich, Frank V.
In: Journal of Biological Chemistry, Vol. 277, No. 6, 08.02.2002, p. 4422-4427.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Agonist-induced force enhancement
T2 - The role of isoforms and phosphorylation of the myosin-targeting subunit of myosin light chain phosphatase
AU - Richards, Christopher T.
AU - Ogut, Ozgur
AU - Brozovich, Frank V.
PY - 2002/2/8
Y1 - 2002/2/8
N2 - The magnitude of agonist-induced Ca2+ sensitization of force is tissue-dependent, but an explanation for this diversity is unknown. Ca2+ sensitization is thought to involve a G-protein-mediated inhibition of myosin light chain phosphatase activity by phosphorylation of the myosin-targeting subunit (MYPT). The MYPT has two isoforms that differ by a central insert, which lies near this phosphorylation site. Expression of MYPT isoforms is both developmentally regulated and tissue-specific. We hypothesized that the presence or absence of the central insert determines the magnitude of agonist-induced Ca2+ sensitization. Throughout development, the chicken aorta exclusively expresses the splice-in MYPT isoform, and guanosine 5′-O-(thiotriphosphate) (GTPγS) produces a significant force enhancement. Early during development, the chicken gizzard expresses the splice-in MYPT isoform, and GTPγS produced a Ca2+ sensitization. In the gizzard coincident with the shift in expression from the splice-in to splice-out MYPT isoform, GTPγS no longer produced force enhancement. In addition, adenosine 5′-O-(thiotriphosphate) (ATPγS) phosphorylated only adult gizzard tissue, the only tissue that did not demonstrate a Ca2+ sensitization. These results suggest that the relative expression of splice-in/splice-out MYPT isoforms determines the magnitude of agonist-induced force enhancement and that MYPT phosphorylation is not required for Ca2+ sensitization.
AB - The magnitude of agonist-induced Ca2+ sensitization of force is tissue-dependent, but an explanation for this diversity is unknown. Ca2+ sensitization is thought to involve a G-protein-mediated inhibition of myosin light chain phosphatase activity by phosphorylation of the myosin-targeting subunit (MYPT). The MYPT has two isoforms that differ by a central insert, which lies near this phosphorylation site. Expression of MYPT isoforms is both developmentally regulated and tissue-specific. We hypothesized that the presence or absence of the central insert determines the magnitude of agonist-induced Ca2+ sensitization. Throughout development, the chicken aorta exclusively expresses the splice-in MYPT isoform, and guanosine 5′-O-(thiotriphosphate) (GTPγS) produces a significant force enhancement. Early during development, the chicken gizzard expresses the splice-in MYPT isoform, and GTPγS produced a Ca2+ sensitization. In the gizzard coincident with the shift in expression from the splice-in to splice-out MYPT isoform, GTPγS no longer produced force enhancement. In addition, adenosine 5′-O-(thiotriphosphate) (ATPγS) phosphorylated only adult gizzard tissue, the only tissue that did not demonstrate a Ca2+ sensitization. These results suggest that the relative expression of splice-in/splice-out MYPT isoforms determines the magnitude of agonist-induced force enhancement and that MYPT phosphorylation is not required for Ca2+ sensitization.
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U2 - 10.1074/jbc.M111047200
DO - 10.1074/jbc.M111047200
M3 - Article
VL - 277
SP - 4422
EP - 4427
JO - Journal of Biological Chemistry
JF - Journal of Biological Chemistry
SN - 0021-9258
IS - 6
ER -