Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Pivot Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Target Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Query: EC:2.7.11.17 (
CaMKII
)
4,029
document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)
Little is known regarding the role of suppressor of cytokine signaling (SOCS) in the control of cytokine signaling in cardiomyocytes. We investigated the consequences of
SOCS2
ablation for leukemia inhibitory factor (LIF)-induced enhancement of intracellular Ca
2+
([Ca
2+
]
i
) transient by performing experiments with cardiomyocytes from
SOCS2
-knockout (ko) mice. Similar levels of SOCS3 transcripts were seen in cardiomyocytes from wild-type and
SOCS2
-ko mice, while SOCS1 mRNA was reduced in
SOCS2
-ko. Immunoprecipitation experiments showed increased SOCS3 association with gp130 receptor in
SOCS2
-ko myocytes. Measurements of Ca
2+
in wild-type myocytes exposed to LIF showed a significant increase in the magnitude of the Ca
2+
transient. This change was absent in LIF-treated
SOCS2
-ko cells. LIF activation of ERK and STAT3 was observed in both wild-type and
SOCS2
-ko cells, indicating that in
SOCS2
-ko, LIF receptors were functional, despite the lack of effect in the Ca
2+
transient. In wild-type cells, LIF-induced increase in [Ca
2+
]
i
and phospholamban Thr17 [PLN(Thr17)] phosphorylation was inhibited by KN-93, indicating a role for
CaMKII
in LIF-induced Ca
2+
raise. LIF-induced phosphorylation of PLN(Thr17) was abrogated in
SOCS2
-ko myocytes. In wild-type cardiomyocytes, LIF treatment increased L-type Ca
2+
current (
I
Ca,L
), a key activator of
CaMKII
in response to LIF. Conversely,
SOCS2
-ko myocytes failed to activate
I
Ca,L
in response to LIF, providing a rationale for the lack of LIF effect on Ca
2+
transient. Our data show that absence of
SOCS2
turns cardiomyocytes unresponsive to LIF-induced [Ca
2+
] raise, indicating that endogenous levels of
SOCS2
are crucial for full activation of LIF signaling in the heart.
...
PMID:Absence of suppressor of cytokine signaling 2 turns cardiomyocytes unresponsive to LIF-dependent increases in Ca
2+
levels. 2812 28
