Mol Biol Cell 2005,
PMID: 15872086
Xie, Zhongjian; Singleton, Patrick A; Bourguignon, Lilly Y W; Bikle, Daniel D
We have previously demonstrated that phospholipase C (PLC)-gamma1 is required for calcium-induced human keratinocyte differentiation. In the present study, we investigated whether the activation of PLC-gamma1 by nonreceptor kinases such as src and fyn plays a role in mediating this process. Our results showed that the combination of dominant negative src and fyn blocked calcium-stimulated PLC-gamma1 activity and human keratinocyte differentiation, whereas each separately has little effect. However, unlike the activation of PLC-gamma1 by epidermal growth factor, calcium-induced activation of PLC-gamma1 was not a result of direct tyrosine phosphorylation. Therefore, we examined an alternative mechanism, in particular phosphatidylinositol 3,4,5-triphosphate (PIP3) formed as a product of phosphatidylinositol 3-kinase (PI3K) activity. PIP3 binds to and activates PLC-gamma1. The combination of dominant negative src and fyn blocked calcium-induced tyrosine phosphorylation of the regulatory subunit of PI3K, p85alpha, and the activity of the catalytic subunit of PI3K. PI3K inhibitors blocked calcium activation of PLC-gamma1 as well as the induction of keratinocyte differentiation markers involucrin and transglutaminase. These data indicate that calcium activates PLC-gamma1 via increased PIP3 formation mediated by c-src- and fyn-activated PI3K. This activation is required for calcium-induced human keratinocyte differentiation.
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Text Mining Data
epidermal growth factor → PLC-gamma1: "
However, unlike the
activation of
PLC-gamma1 by
epidermal growth factor , calcium induced activation of PLC-gamma1 was not a result of direct tyrosine phosphorylation
"
PLC-gamma1 → PIP3: "
PIP3 binds to and activates PLC-gamma1
"
involucrin → PI3K: "
PI3K inhibitors blocked calcium activation of PLC-gamma1 as well as the induction of keratinocyte differentiation markers involucrin and transglutaminase
"
PLC-gamma1 → PI3K: "
PI3K inhibitors blocked calcium activation of PLC-gamma1 as well as the induction of keratinocyte differentiation markers involucrin and transglutaminase
"
PIP3 → PI3K: "
These data indicate that calcium activates PLC-gamma1 via increased PIP3 formation mediated by c-src- and fyn activated PI3K
"
Manually curated Databases
-
NCI Pathway Database E-cadherin signaling in keratinocytes:
E-cadherin/Ca2+/beta catenin-gamma catenin/alpha catenin/p120 catenin complex (CDH1-CTNNB1_JUP-CTNNA1-CTNND1)
→
PI3K complex (PIK3CA-PIK3R1)
(modification, activates)
Evidence: assay, physical interaction
-
NCI Pathway Database E-cadherin signaling in keratinocytes:
E-cadherin/beta catenin-gamma catenin complex (CDH1-CTNNB1_JUP)
→
alpha catenin (CTNNA1)
(modification, collaborate)
Evidence: assay, physical interaction, other species
-
NCI Pathway Database E-cadherin signaling in keratinocytes:
E-cadherin/beta catenin-gamma catenin complex (CDH1-CTNNB1_JUP)
→
Src (SRC)
(modification, collaborate)
Evidence: assay, physical interaction, other species
-
NCI Pathway Database E-cadherin signaling in keratinocytes:
E-cadherin/beta catenin-gamma catenin complex (CDH1-CTNNB1_JUP)
→
E-cadherin/beta catenin-gamma catenin/alpha catenin/p120 catenin complex (CDH1-CTNNB1_JUP-CTNNA1-CTNND1)
(modification, collaborate)
Evidence: assay, physical interaction, other species
-
NCI Pathway Database E-cadherin signaling in keratinocytes:
E-cadherin/beta catenin-gamma catenin complex (CDH1-CTNNB1_JUP)
→
Fyn (FYN)
(modification, collaborate)
Evidence: assay, physical interaction, other species
-
NCI Pathway Database E-cadherin signaling in keratinocytes:
E-cadherin/beta catenin-gamma catenin complex (CDH1-CTNNB1_JUP)
→
p120 catenin (CTNND1)
(modification, collaborate)
Evidence: assay, physical interaction, other species
-
NCI Pathway Database E-cadherin signaling in keratinocytes:
alpha catenin (CTNNA1)
→
Src (SRC)
(modification, collaborate)
Evidence: assay, physical interaction, other species
-
NCI Pathway Database E-cadherin signaling in keratinocytes:
alpha catenin (CTNNA1)
→
E-cadherin/beta catenin-gamma catenin/alpha catenin/p120 catenin complex (CDH1-CTNNB1_JUP-CTNNA1-CTNND1)
(modification, collaborate)
Evidence: assay, physical interaction, other species
-
NCI Pathway Database E-cadherin signaling in keratinocytes:
alpha catenin (CTNNA1)
→
Fyn (FYN)
(modification, collaborate)
Evidence: assay, physical interaction, other species
-
NCI Pathway Database E-cadherin signaling in keratinocytes:
alpha catenin (CTNNA1)
→
p120 catenin (CTNND1)
(modification, collaborate)
Evidence: assay, physical interaction, other species
-
NCI Pathway Database E-cadherin signaling in keratinocytes:
Src (SRC)
→
E-cadherin/beta catenin-gamma catenin/alpha catenin/p120 catenin complex (CDH1-CTNNB1_JUP-CTNNA1-CTNND1)
(modification, activates)
Evidence: assay, physical interaction, other species
-
NCI Pathway Database E-cadherin signaling in keratinocytes:
Src (SRC)
→
Fyn (FYN)
(modification, activates)
Evidence: assay, physical interaction, other species
-
NCI Pathway Database E-cadherin signaling in keratinocytes:
Src (SRC)
→
p120 catenin (CTNND1)
(modification, activates)
Evidence: assay, physical interaction, other species
-
NCI Pathway Database E-cadherin signaling in keratinocytes:
E-cadherin/beta catenin-gamma catenin/alpha catenin/p120 catenin complex (CDH1-CTNNB1_JUP-CTNNA1-CTNND1)
→
p120 catenin (CTNND1)
(modification, collaborate)
Evidence: assay, physical interaction, other species
-
NCI Pathway Database E-cadherin signaling in keratinocytes:
Fyn (FYN)
→
p120 catenin (CTNND1)
(modification, activates)
Evidence: assay, physical interaction, other species
In total, 37 gene pairs are associated to this article in curated databases