Direct binding of RalA to PKCη and its crucial role in morphological change during keratinocyte differentiation

Yasuhito Shirai, Shoko Morioka, Megumi Sakuma, Ken Ichi Yoshino, Chihiro Otsujia, Norio Sakai, Kaori Kashiwagi, Kazuhiro Chida, Ryutaro Shirakawa, Hisanori Horiuchi, Chikako Nishigori, Takehiko Ueyama, Naoaki Saito

Research output: Contribution to journalArticlepeer-review

9 Citations (Scopus)


During differentiation, keratinocytes undergo a dramatic shape change from small and round to large and flat, in addition to production of proteins necessary for the formation of epidermis. It has been shown that protein kinase C (PKC) η is crucial for keratinocyte differentiation. However, its role in this process has yet to be fully elucidated. Here, we show that catalytic activity is not necessary for enlarged and flattened morphology of human keratinocytes induced by overexpression of PKCη, although it is important for gene expression of the marker proteins. In addition, we identify the small G protein RalA as a binding partner of PKCη, which binds to the C1 domain, an indispensable region for the morphological change. The binding led activation of RalA and actin depolymerization associated with keratinocyte differentiation. siRNA techniques proved that RalA is involved in not only the keratinocyte differentiation induced by PKCη overexpression but also normal keratinocyte differentiation induced by calcium and cholesterol sulfate. These results provide a new insight into the molecular mechanism of cytoskeletal regulation leading to drastic change of cell shape.

Original languageEnglish
Pages (from-to)1340-1352
Number of pages13
JournalMolecular Biology of the Cell
Issue number8
Publication statusPublished - 2011 Apr 15


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