Protein kinase Cdelta-mediated phosphorylation of phospholipase D controls integrin-mediated cell spreading.

Abstract:

:Integrin signaling plays critical roles in cell adhesion, spreading, and migration, and it is generally accepted that to regulate these integrin functions accurately, localized actin remodeling is required. However, the molecular mechanisms that control the targeting of actin regulation molecules to the proper sites are unknown. We previously demonstrated that integrin-mediated cell spreading and migration on fibronectin are dependent on the localized activation of phospholipase D (PLD). However, the mechanism underlying PLD activation by integrin is largely unknown. Here we demonstrate that protein kinase Cδ (PKCδ) is required for integrin-mediated PLD signaling. After integrin stimulation, PKCδ is activated and translocated to the edges of lamellipodia, where it colocalizes with PLD2. The abrogation of PKCδ activity inhibited integrin-induced PLD activation and cell spreading. Finally, we show that Thr566 of PLD2 is directly phosphorylated by PKCδ and that PLD2 mutation in this region prevents PLD2 activation, PLD2 translocation to the edge of lamellipodia, Rac translocation, and cell spreading after integrin activation. Together, these results suggest that PKCδ is a primary regulator of integrin-mediated PLD activation via the direct phosphorylation of PLD, which is essential for directing integrin-induced cell spreading.

journal_name

Mol Cell Biol

authors

Chae YC,Kim KL,Ha SH,Kim J,Suh PG,Ryu SH

doi

10.1128/MCB.00443-10

subject

Has Abstract

pub_date

2010-11-01 00:00:00

pages

5086-98

issue

21

eissn

0270-7306

issn

1098-5549

pii

MCB.00443-10

journal_volume

30

pub_type

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