scholarly journals Localization of Atypical Protein Kinase C Isoforms into Lysosome-Targeted Endosomes through Interaction with p62

1998 ◽  
Vol 18 (5) ◽  
pp. 3069-3080 ◽  
Author(s):  
Pilar Sanchez ◽  
Guillermo De Carcer ◽  
Ignacio V. Sandoval ◽  
Jorge Moscat ◽  
María T. Diaz-Meco

ABSTRACT An increasing number of independent studies indicate that the atypical protein kinase C (PKC) isoforms (aPKCs) are critically involved in the control of cell proliferation and survival. The aPKCs are targets of important lipid mediators such as ceramide and the products of the PI 3-kinase. In addition, the aPKCs have been shown to interact with Ras and with two novel proteins, LIP (lambda-interacting protein; a selective activator of λ/ιPKC) and the product ofpar-4 (a gene induced during apoptosis), which is an inhibitor of both λ/ιPKC and ζPKC. LIP and Par-4 interact with the zinc finger domain of the aPKCs where the lipid mediators have been shown to bind. Here we report the identification of p62, a previously described phosphotyrosine-independent p56 lck SH2-interacting protein, as a molecule that interacts potently with the V1 domain of λ/ιPKC and, albeit with lower affinity, with ζPKC. We also show in this study that ectopically expressed p62 colocalizes perfectly with both λ/ιPKC and ζPKC. Interestingly, the endogenous p62, like the ectopically expressed protein, displays a punctate vesicular pattern and clearly colocalizes with endogenous λ/ιPKC and endogenous ζPKC. P62 colocalizes with Rab7 and partially with lamp-1 and limp-II as well as with the epidermal growth factor (EGF) receptor in activated cells, but not with Rab5 or the transferrin receptor. Of functional relevance, expression of dominant negative λ/ιPKC, but not of the wild-type enzyme, severely impairs the endocytic membrane transport of the EGF receptor with no effect on the transferrin receptor. These findings strongly suggest that the aPKCs are anchored by p62 in the lysosome-targeted endosomal compartment, which seems critical for the control of the growth factor receptor trafficking. This is particularly relevant in light of the role played by the aPKCs in mitogenic cell signaling events.

2001 ◽  
Vol 276 (11) ◽  
pp. 7709-7712 ◽  
Author(s):  
Marie W. Wooten ◽  
M. Lamar Seibenhener ◽  
Vidya Mamidipudi ◽  
Maria T. Diaz-Meco ◽  
Philip A. Barker ◽  
...  

1999 ◽  
Vol 2 (1) ◽  
pp. 28-31 ◽  
Author(s):  
M.Lamar Seibenhener ◽  
Jennifer Roehm ◽  
Wendy O. White ◽  
Kimberly B.W. Neidigh ◽  
Michel L. Vandenplas ◽  
...  

2000 ◽  
Vol 275 (34) ◽  
pp. 26390-26395 ◽  
Author(s):  
Ko Kotani ◽  
Wataru Ogawa ◽  
Mitsuru Hashiramoto ◽  
Tetsuo Onishi ◽  
Shigeo Ohno ◽  
...  

2000 ◽  
Vol 20 (13) ◽  
pp. 4494-4504 ◽  
Author(s):  
Marie W. Wooten ◽  
M. Lamar Seibenhener ◽  
Kimberly B. W. Neidigh ◽  
Michel L. Vandenplas

ABSTRACT The pathway by which atypical protein kinase C (aPKC) contributes to nerve growth factor (NGF) signaling is poorly understood. We previously reported that in PC12 cells NGF-induced activation of mitogen-activated protein kinase (MAPK) occurs independently of classical and nonclassical PKC isoforms, whereas aPKC isoforms were shown to be required for NGF-induced differentiation. NGF-induced activation of PKC-ι was observed to be dependent on phosphatidylinositol 3-kinase (PI3K) and led to coassociation of PKC-ι with Ras and Src. Expression of dominant negative mutants of either Src (DN2) or Ras (Asn-17) impaired activation of PKC-ι by NGF. At the level of Raf-1, neither PKC-ι nor PI3 kinase was required for activation; however, PKC-ι could weakly activate MEK. Inhibitors of PKC-ι activity and PI3K had no effect on NGF-induced MAPK or p38 activation but reduced NGF-stimulated c-Jun N-terminal kinase activity. Src, PI3K, and PKC-ι were likewise required for NGF-induced NF-κB activation and cell survival, whereas Ras was not required for either survival or NF-κB activation but was required for differentiation. IKK existed as a complex with PKC-ι, Src and IκB. Consistent with a role for Src in regulating NF-κB activation, an absence of Src activity impaired recruitment of PKC-ι into an IKK complex and markedly impaired NGF-induced translocation of p65/NF-κB to the nucleus. These findings reveal that in PC12 cells, aPKCs comprise a molecular switch to regulate differentiation and survival responses coupled downstream to NF-κB. On the basis of these findings, Src emerges as a critical upstream regulator of both PKC-ι and the NF-κB pathway.


2002 ◽  
Vol 14 (4) ◽  
pp. 359-363 ◽  
Author(s):  
Michel L Vandenplas ◽  
Vidya Mamidipudi ◽  
M Lamar Seibenhener ◽  
Marie W Wooten

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