Coordinated movement of RACK1 with activated betaIIPKC.
Protein kinase C (PKC) isozymes move upon activation from one intracellular site to another. PKC-binding proteins, such as receptors for activated C kinase (RACKs), play an important role in regulating the localization and diverse functions of PKC isozymes. RACK1, the receptor for activated betaIIPKC, determines the localization and functional activity of betaIIPKC. However, the mechanism by which RACK1 localizes activated betaIIPKC is not known. Here, we provide evidence that the intracellular localization of RACK1 changes in response to PKC activation. In Chinese hamster ovary cells transfected with the dopamine D2L receptor and in NG108-15 cells, PKC activation by either phorbol ester or a dopamine D2 receptor agonist caused the movement of RACK1. Moreover, PKC activation resulted in the in situ association and movement of RACK1 and betaIIPKC to the same intracellular sites. Time course studies indicate that PKC activation induces the association of the two proteins prior to their co-movement. We further show that association of RACK1 and betaIIPKC is required for the movement of both proteins. Our results suggest that RACK1 is a PKC shuttling protein that moves betaIIPKC from one intracellular site to another.
Ron
D
D
Department of Neurology, University of California, San Francisco, California 94110-3518, USA. dorit@itsa.ucsf.edu
Jiang
Z
Z
Yao
L
L
Vagts
A
A
Diamond
I
I
Gordon
A
A
D000818:Animals; D001693:Biological Transport, Active; D016466:CHO Cells; D006224:Cricetinae; D004789:Enzyme Activation; D006056:Golgi Apparatus / Q000378:metabolism; D007150:Immunohistochemistry; D011493:Protein Kinase C / Q000378:metabolism*; D000075370:Receptors for Activated C Kinase; D011956:Receptors, Cell Surface / Q000378:metabolism*
D000075370:Receptors for Activated C Kinase; D011956:Receptors, Cell Surface; C061570:protein kinase N; D011493:Protein Kinase C