Abstract/Details

Protein Kinase D Signaling Through Substrate Phosphorylation in Endocytic Trafficking


2011 2011

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Abstract (summary)

Mammalian Protein Kinase D (PKD) is a family of three serine/threonine kinases classified as Calcium/Calmodulin-dependent Kinases. PKD signaling is regulated by Phospholipase C (PLC)-dependent production of diacylglycerol (DAG), which recruits PKD as well as its upstream kinase Protein Kinase C (PKC) to the plasma or Golgi membranes (Zugaza et al., 1996). The binding of DAG to the PKD cysteine rich domains facilitates phosphorylation of the PKD activation loop by PKC. Though PKD activity initiates a number of cellular processes including proliferation and survival (Rykx et al., 2003; Van Lint et al., 2002), it is best characterized as a critical regulator of Golgi trafficking. Through phosphorylation of its substrate PI4KinaseIII3β, PKD controls the fission of cargo-containing membranes at the trans-Golgi network (Rykx et al., 2003).

Recently, studies have emerged which describe a role for PKD endocytic trafficking. PKD mediates signals through platelet-derived growth factor (PDGF) to control the recycling of αvβ3 integrin (Woods et al., 2004). Here, we use a PKD substrate-directed phosphorylation-specific antibody (PKD pMOTIF) to identify Rabaptin-5 as a novel signaling effector of PKD. PKD phosphorylation of Rabaptin-5 is required for PDGF-induced αvβ3 integrin recycling. Additionally, we report that the PKD-Rabaptin-5 signaling pathway controls the persistent migration of fibroblasts. These findings provide a mechanism by which PKD-regulated trafficking extends to the endocytic compartment and exerts controls over processes required for cell motility.

Indexing (details)


Subject
Molecular biology;
Cellular biology
Classification
0307: Molecular biology
0379: Cellular biology
Identifier / keyword
Biological sciences; Calcium kinases; Calmodulin kinases; Endocytic trafficking; Phosphorylation; Protein kinase D; Signaling
Title
Protein Kinase D Signaling Through Substrate Phosphorylation in Endocytic Trafficking
Author
Cohick, Claudine Virginie
Number of pages
124
Publication year
2011
Degree date
2011
School code
0084
Source
DAI-B 72/09, Dissertation Abstracts International
Place of publication
Ann Arbor
Country of publication
United States
ISBN
9781124737096
Advisor
Toker, Alex
University/institution
Harvard University
University location
United States -- Massachusetts
Degree
Ph.D.
Source type
Dissertations & Theses
Language
English
Document type
Dissertation/Thesis
Dissertation/thesis number
3462485
ProQuest document ID
879086269
Copyright
Database copyright ProQuest LLC; ProQuest does not claim copyright in the individual underlying works.
Document URL
http://search.proquest.com/docview/879086269
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