Gene interactions and pathways from curated databases and text-mining
Mol Biol Cell 2005, PMID: 15872086

Calcium-induced human keratinocyte differentiation requires src- and fyn-mediated phosphatidylinositol 3-kinase-dependent activation of phospholipase C-gamma1.

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