Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.1.4.3 (phospholipase C)
 18,461 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

TWIK-related acid-sensitive K(+) (TASK) channels produce background K(+) currents. We elucidated that TASK1 channels in rat adrenal medullary cells and PC12 cells are internalized in a clathrin-dependent manner in response to nerve growth factor (NGF). Here, the molecular mechanism for this internalization in PC12 cells was explored. The combination of enzyme inhibitors with tropomyosin receptor kinase A mutants revealed that the internalization was mediated by both phospholipase C and phosphatidylinositol 3-kinase pathways that converge on protein kinase C with the consequent activation of Src, a nonreceptor tyrosine kinase. The NGF-induced endocytosis of TASK1 channels did not occur in the presence of the Src inhibitor or with the expression of a kinase-dead Src mutant. Additionally, NGF induced a transient colocalization of Src with the TASK1 channel, but not the TASK1 mutant, in which tyrosine at 370 was replaced with phenylalanine. This TASK1 mutant showed no increase in tyrosine phosphorylation and markedly diminished internalization in response to NGF. We concluded that NGF induces endocytosis of TASK1 channels via tyrosine phosphorylation in its carboxyl terminus.
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PMID:Src mediates endocytosis of TWIK-related acid-sensitive K+ 1 channels in PC12 cells in response to nerve growth factor. 2608 7

TWIK-related acid-sensitive K+ (TASK) homomeric channels, TASK1 and TASK3, are present in PC12 cells. The channels do not heteromerize due plausibly to a lack of p11 protein. Single-channel recording reveals that most of the rat carotid body (CB) glomus cells express heteromeric TASK1-TASK3 channels, but the presence of p11 in glomus cells has not yet been verified. TASK1, but not TASK3, binds to p11, which has a retention signal for the endoplasmic reticulum. We hypothesized that p11 could facilitate heteromeric TASK1-TASK3 formation in glomus cells. We investigated this hypothesis in isolated immunocytochemically identified rat CB glomus cells. The findings were that glomus cells expressed p11-like immunoreactive (IR) material, and TASK1- and TASK3-like IR material mainly coincided in the cytoplasm. The proximity ligation assay showed that TASK1 and TASK3 heteromerized. In separate experiments, supporting evidence for the major role of p11 for channel heteromerization was provided in PC12 cells stimulated by nerve growth factor. p11 production took place there via multiple signaling pathways comprising mitogen-activated protein kinase and phospholipase C, and heteromeric TASK1-TASK3 channels were formed. We conclude that p11 is expressed and TASK1 and TASK3 heteromerize in rat CB glomus cells.
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PMID:Expression of p11 and Heteromeric TASK Channels in Rat Carotid Body Glomus Cells and Nerve Growth Factor-differentiated PC12 Cells. 3288 17