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

Abstract:

: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.

journal_name

Mol Biol Cell

authors

Shirai Y,Morioka S,Sakuma M,Yoshino K,Otsuji C,Sakai N,Kashiwagi K,Chida K,Shirakawa R,Horiuchi H,Nishigori C,Ueyama T,Saito N

doi

10.1091/mbc.E10-09-0754

subject

Has Abstract

pub_date

2011-04-15 00:00:00

pages

1340-52

issue

8

eissn

1059-1524

issn

1939-4586

pii

mbc.E10-09-0754

journal_volume

22

pub_type

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