In:
BioMed Research International, Hindawi Limited, Vol. 2016 ( 2016), p. 1-11
Kurzfassung:
Extracellular calcium is a major regulator of keratinocyte differentiation in vitro and appears to play that role in vivo, but the mechanism is unclear. We have previously demonstrated that, following calcium stimulation, PIP5K1 α is recruited by the E-cadherin- β -catenin complex to the plasma membrane where it provides the substrate PIP2 for both PI3K and PLC- γ 1. This signaling pathway is critical for calcium-induced generation of second messengers including IP3 and intracellular calcium and keratinocyte differentiation. In this study, we explored the upstream regulatory mechanism by which calcium activates PIP5K1 α and the role of this activation in calcium-induced keratinocyte differentiation. We found that treatment of human keratinocytes in culture with calcium resulted in an increase in serine dephosphorylation and PIP5K1 α activation. PP1 knockdown blocked extracellular calcium-induced increase in serine dephosphorylation and activity of PIP5K1 α and induction of keratinocyte differentiation markers. Knockdown of PLC- γ 1, the downstream effector of PIP5K1 α , blocked upstream dephosphorylation and PIP5K1 α activation induced by calcium. Coimmunoprecipitation revealed calcium induced recruitment of PP1 to the E-cadherin-catenin-PIP5K1 α complex in the plasma membrane. These results indicate that PP1 is recruited to the extracellular calcium-dependent E-cadherin-catenin-PIP5K1 α complex in the plasma membrane to activate PIP5K1 α , which is required for PLC- γ 1 activation leading to keratinocyte differentiation.
Materialart:
Online-Ressource
ISSN:
2314-6133
,
2314-6141
DOI:
10.1155/2016/3062765
Sprache:
Englisch
Verlag:
Hindawi Limited
Publikationsdatum:
2016
ZDB Id:
2698540-8