Protein kinase Calpha can undergo membrane localization via an alternative phosphatidylinositol 4,5-bisphosphate-dependent pathway.
Protein kinase Calpha (PKCalpha) activation is known to be dependent on the metabolic product of phosphatidylinositol 4,5-bisphosphate (PIP2) by phospholipase C (PLC). Here we report that fibroblasts may have an additional PIP2-dependent mechanism for membrane localization of PKCalpha. We observed PKCalpha membrane localization in both wild type and PLCgamma1 -/- mouse embryonic fibroblasts. Treatment of cells with a specific PLC inhibitor U73122 resulted in increased PIP2 levels and enhanced membrane localization of PKCalpha. PKCalpha levels in the membrane fraction decreased following incubation with PLCgamma, but increased following treatment with U73122 or addition of exogenous PIP2 in vitro. In addition, PKCalpha interacted with PIP2-conjugate bead and mixed micelles containing PIP2. Finally, we found that PIP2 is involved in syndecan-4-mediated membrane localization of PKCalpha. Taken together, these data suggest that PIP2 might contribute to directly regulating the membrane localization of PKCalpha.
Son
Hyowon
H
Department of Life Sciences, Division of Molecular Life Sciences and Center for Cell Signaling Research, Ewha Womans University, Daehyun-dong, Seodaemoon-Gu, Seoul, Republic of Korea.
Lim
Yangmi
Y
Kim
Jinsook
J
Park
Haein
H
Choi
Sojoong
S
Han
Innoc
I
Kim
Won-Seok
WS
Park
Sungsu
S
Bae
Yunsoo
Y
Oh
Eok-Soo
ES
D000818:Animals; D019556:COS Cells; D002462:Cell Membrane / Q000378:metabolism*; D002522:Chlorocebus aethiops; D005347:Fibroblasts / Q000378:metabolism*; D051379:Mice; D019269:Phosphatidylinositol 4,5-Diphosphate / Q000378:metabolism*; D051571:Protein Kinase C-alpha / Q000378:metabolism*; D051381:Rats; D015398:Signal Transduction / Q000502:physiology*; D013347:Subcellular Fractions / Q000378:metabolism*
D019269:Phosphatidylinositol 4,5-Diphosphate; D051571:Protein Kinase C-alpha