Targeting of Protein Kinase Cα to Caveolae

Mineo, Chieko; Ying, Yun Shu; Chapline, Christine; Jaken, Susan; Anderson, Richard G. W.

doi:10.1083/jcb.141.3.601

Cited by 172 publications

(132 citation statements)

References 28 publications

(72 reference statements)

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Section: P Upla Et Alsupporting

confidence: 55%

“…A similar small increase in the phosphorylation of PKC␣ was seen after the cells were exposed to EV1 or antibodies forming ␣2␤1 clusters. Previous studies support the idea that PKC␣ is needed for caveola-related signaling functions (Smart et al, 1994;Mineo et al, 1998).We have identified the formation of ␣2␤1 integrin clusters as a key event leading to the relocation of ␣2␤1 to caveolae. Furthermore, ␣2␤1 clusters trigger the internalization of caveolae (the process has been summarized in Figure 8).…”

supporting

confidence: 54%

“…Interestingly, PKC␣ may directly bind to the cytoplasmic domain of integrin ␤1 subunit (Ng et al, 1999a). Furthermore, PKC␣ seems to be a resident protein of caveolae, which are major cell surface locations for this enzyme (Smart et al, 1994;Mineo et al, 1998). In caveolae PKC␣ might be constantly active (Smart et al, 1994;Mineo et al, 1998).…”

Section: P Upla Et Almentioning

confidence: 99%

“…Furthermore, PKC␣ seems to be a resident protein of caveolae, which are major cell surface locations for this enzyme (Smart et al, 1994;Mineo et al, 1998). In caveolae PKC␣ might be constantly active (Smart et al, 1994;Mineo et al, 1998). Accordingly, control SAOS-␣2␤1 cells contained phosphorylated PKC␣, and PMA could only slightly increase its phosphorylation.…”

mentioning

confidence: 99%

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Clustering Induces a Lateral Redistribution of α2β1 Integrin from Membrane Rafts to Caveolae and Subsequent Protein Kinase C-dependent Internalization

Upla

Marjomäki

Kankaanpää

et al. 2004

MBoC

151

186

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Integrin ␣2␤1 mediates the binding of several epithelial and mesenchymal cell types to collagen. The composition of the surrounding plasma membrane, especially caveolin-1-and cholesterol-containing membrane structures called caveolae, may be important to integrin signaling. On cell surface ␣2␤1 integrin was located in the raft like membrane domain, rich in GPI-anchored proteins, rather than in caveolae. However, when antibodies were used to generate clusters of ␣2␤1 integrin, they started to move laterally on cell surface along actin filaments. During the lateral movement small clusters fused together. Finally ␣2␤1 integrin was found inside caveolae and subsequently internalized into caveosome-like perinuclear structures. The internalization process, unlike cluster formation or lateral redistribution, was dependent on protein kinase C␣ activity. Caveolae are known to be highly immobile structures and ␣2␤1 integrin clusters represent a previously unknown mechanism to activate endocytic trafficking via caveolae. The process was specific to ␣2␤1 integrin, because the antibody-mediated formation of ␣V integrin clusters activated their internalization in coated vesicles and early endosomes. In addition to natural ligands human echovirus-1 (EV1) gains entry into the cell by binding to ␣2␤1 and taking advantage of ␣2␤1 internalization via caveolae. INTRODUCTIONCaveolae are cave-like invaginations of the cell surface (for reviews see Kurzchalia and Parton, 1999;Parton 2003). They have been described as highly immobile and not involved in constitutive endocytic trafficking (Thomsen et al., 2002). Their internalization can be activated, for example, by the phosphatase inhibitor okadaic acid (Parton et al., 1994). In endothelial cells the interaction of albumin docking protein gp60 and caveolin-1 initiates the endocytosis of caveolae (Minshall et al., 2000). Caveolins are membrane proteins that are molecular markers of caveolae and shown to be crucial for the formation of these structures (Fra et al., 1995). Caveolins can be associated with cell surface growth factor receptors (Couet et al., 1997) and cell adhesion receptors (Wary et al., 1996(Wary et al., , 1998Wei et al., 1999) and caveolae might therefore play a role in cellular signaling. In addition, caveolae have been suggested to participate in the uptake of folate by pinocytosis, but this is still under discussion (Parton, 2003). Caveolin-deficient mice have given novel insight into the function of caveolae. Caveolin-1 gene knockout leads to pulmonary defects, vasoconstriction, or dilatation abnormalities and resistance to diet-induced obesity (Drab et al., 2001;Razani et al., 2001;Schubert et al., 2001;Sotgia et al., 2002;Razani et al., 2002). Simian virus 40 (SV40) has been shown to be internalized through caveolae and detailed studies focused on the virus entry mechanism have produced a lot of new information about the biology of caveolae (Pelkmans et al., 2001. We have recently shown that human echovirus 1 (EV1) is another virus using caveolae in its entry (Mar...

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Section: P Upla Et Alsupporting

confidence: 55%

supporting

confidence: 54%

Section: P Upla Et Almentioning

confidence: 99%

mentioning

confidence: 99%

See 2 more Smart Citations

Clustering Induces a Lateral Redistribution of α2β1 Integrin from Membrane Rafts to Caveolae and Subsequent Protein Kinase C-dependent Internalization

Upla

Marjomäki

Kankaanpää

et al. 2004

MBoC

151

186

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“…64,65 RACK1 is a scaffold for PKCα, which in earlier studies was shown to regulate p120GAP activity in T lymphocytes, 99 but also might target p120GAP to cholesterol-rich membrane domains, such as caveolae, in other settings. 100 By extending the previous work from Davis et al, 101 we demonstrated that AnxA6 binds to the CALB/C2 domain of p120GAP to facilitate the Ca 2+ -dependent recruitment of p120GAP to inactivate H-Ras at the plasma membrane upon EGFR activation. 30,39,40 For a more comprehensive description of the AnxA6/ p120GAP complex and its involvement in Ras inactivation upon EGFR activation, we refer the reader to previous reviews from our laboratories.…”

Section: Nf1mentioning

confidence: 96%

Differential Regulation of RasGAPs in Cancer

et al. 2011

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Ever since their discovery as cellular counterparts of viral oncogenes more than 25 years ago, much progress has been made in understanding the complex networks of signal transduction pathways activated by oncogenic Ras mutations in human cancers. The activity of Ras is regulated by nucleotide exchange factors (GEFs) and GTPase activating proteins (GAPs), and much emphasis has been put into the biochemical and structural analysis of the Ras/GAP complex. The mechanisms by which GAPs catalyze Ras-GTP hydrolysis have been clarified and revealed that oncogenic Ras mutations confer resistance to GAPs and remain constitutively active. However, it is yet unclear how cells coordinate the large and divergent GAP protein family to promote Ras inactivation and ensure a certain biological response. Different domain arrangements in GAPs to create differential protein-protein and protein-lipid interactions are probably key factors determining the inactivation of the 3 Ras isoforms H-, K-, and N-Ras and their effector pathways. In recent years, in vitro as well as cell-and animal-based studies examining GAP activity, localization, interaction partners, and expression profiles have provided further insights into Ras inactivation and revealed characteristics of several GAPs to exert specific and distinct functions. This review aims to summarize knowledge on the cell biology of RasGAP proteins that potentially contributes to differential regulation of spatiotemporal Ras signaling.

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