Interaction of Protein Kinase C Isozymes with Rho GTPases

Slater, Simon J.; Seiz, Jodie L; Stagliano, Brigid A.; Stubbs, Christopher D.

doi:10.1021/bi001654n

Cited by 70 publications

(81 citation statements)

References 50 publications

(85 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Since some Gq coupled receptors have been reported to also interact with G 12/13 signaling [38][39][40][41], it is conceivable that G 12/13 signaling is activated following P2Y 6 receptor stimulation. It was also shown that Rho signaling activated PKCs [18,42,43]. These findings suggest that the activation of Rho and PKC is induced by P2Y 6 receptor activation and regulates F-actin aggregation.…”

Section: Udp-induced Vasp Phosphorylation At Ser157 Is Mediated By Rhmentioning

confidence: 81%

See 1 more Smart Citation

Involvement of vasodilator-stimulated phosphoprotein in UDP-induced microglial actin aggregation via PKC- and Rho-dependent pathways

Kataoka¹,

Koga²,

Uesugi³

et al. 2011

Purinergic Signalling

View full text Add to dashboard Cite

Microglia are major immunocompetent cells in the central nervous system and retain highly dynamic motility. The processes which allow these cells to move, such as chemotaxis and phagocytosis, are considered part of their functions and are closely related to purinergic signaling. Previously, we reported that the activation of the P2Y 6 receptor by UDP stimulation in microglia evoked dynamic cell motility which enhanced their phagocytic capacity, as reported by Koizumi et al. (Nature 446 (7139):1091-1095. These responses require actin cytoskeletal rearrangement, which is seen after UDP stimulation. However, the intracellular signaling pathway has not been defined. In this study, we found that UDP in rat primary microglia rapidly induced the transient phosphorylation at Ser157 of vasodilator-stimulated phosphoprotein (VASP). VASP, one of actin binding protein, accumulated at the plasma membrane where filamentous (F)-actin aggregated in a time-dependent manner. The phosphorylation of VASP was suppressed by inhibition of PKC. UDP-induced local actin aggregations were also abrogated by PKC inhibitors. The Rho inhibitor CT04 and the expression of p115-RGS, which suppresses G 12/13 signaling, attenuated UDP-induced phosphorylation of VASP and actin aggregation. These results indicate that PKC-and Rho-dependent phosphorylation of VASP is involved in UDP-induced actin aggregation of microglia.

show abstract

Section: Udp-induced Vasp Phosphorylation At Ser157 Is Mediated By Rhmentioning

confidence: 81%

“…We examined the involvement of Rho GTPases because it was reported that PKC was a downstream target of RhoA [18] and VASP phosphorylation was regulated by RhoA activation [19]. We use the Rho inhibitor CT04 to inactivate RhoA, RhoB and RhoC.…”

Section: Udp-induced Actin Aggregation and Vasp Phosphorylation Were mentioning

confidence: 99%

Involvement of vasodilator-stimulated phosphoprotein in UDP-induced microglial actin aggregation via PKC- and Rho-dependent pathways

Kataoka¹,

Koga²,

Uesugi³

et al. 2011

Purinergic Signalling

View full text Add to dashboard Cite

show abstract

“…The Rho family and their upstream or downstream factors have been implicated in various cellular functions such as regulation of actin filament reorganization and exocytosis (27,28). In mast and chromaffin cells, one or more members of the Rho family play an active role in the exocytotic process (27,28,59,60).…”

Section: Discussionmentioning

confidence: 99%

“…In mast and chromaffin cells, one or more members of the Rho family play an active role in the exocytotic process (27,28,59,60). In addition, Cdc42 and Rac control regulated secretion in pancreatic ␤-cells (61).…”

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

The Role of Protein Kinase D in Neurotensin Secretion Mediated by Protein Kinase C-α/-δ and Rho/Rho Kinase

O’Connor

Hellmich

et al. 2004

Journal of Biological Chemistry

View full text Add to dashboard Cite

Neurotensin (NT) is a gut peptide that plays an important role in gastrointestinal (GI) secretion, motility, and growth as well as the proliferation of NT receptor positive cancers. Secretion of NT is regulated by phorbol ester-sensitive protein kinase C (PKC) isoforms-␣ and -␦ and may involve protein kinase D (PKD). The purpose of our present study was: (i) to define the role of PKD in NT release from BON endocrine cells and (ii) to delineate the upstream signaling mechanisms mediating this effect. Here, we demonstrate that small interfering RNA (siRNA) targeted against PKD dramatically inhibited both basal and PMA-stimulated NT secretion; NT release is significantly increased by overexpression of PKD. PKC-␣ and -␦ siRNA attenuated PKD activity, whereas overexpression of PKC-␣ and -␦ enhanced PKD activity. Rho kinase (ROK) siRNA significantly inhibited NT secretion, whereas overexpression of ROK␣ effectively increased NT release. Rho protein inhibitor C3 dramatically inhibited both NT secretion and PKD activity. In conclusion, our results demonstrate that PKD activation plays a central role in NT peptide secretion; upstream regulators of PKD include PKC-␣ and -␦ and Rho/ROK. Importantly, our results identify novel signaling pathways, which culminate in gut peptide release.Regulatory hormones, localized to specialized endocrine cells in the small bowel, control numerous physiological functions of the gastrointestinal (GI) tract including secretion, motility, and mucosal growth (1). The gut peptide neurotensin (NT), 1 a tridecapeptide localized to enteroendocrine cells (N cells) of the distal small bowel (2, 3), facilitates fatty acid translocation (4), affects gut motility (5), and stimulates growth of normal gut mucosa (6, 7). In addition to its trophic effects on normal GI tissues, NT stimulates proliferation of certain pancreatic, colonic, and prostatic cancers bearing NT receptors (NTR) (8). Although the mechanisms for pancreatic hormone release have been well characterized (9), the signal transduction pathways regulating stimuli-induced gut hormone secretion are not entirely understood. One reason for this paucity in our understanding is the relative lack of useful in vitro models that recapitulate in vivo properties of intestinal endocrine cells.The BON endocrine cell line was established from a human pancreatic carcinoid tumor and characterized in our laboratory (10). These cells have served as an invaluable in vitro model for hormone secretion studies. Similar to the terminally differentiated N cell of the small bowel, BON cells express high levels of NT/neuromedin N mRNA, synthesize and secrete NT peptide, and process the NT/neuromedin N precursor protein in a fashion identical to that of the normal intestine (11). BON cells exhibit morphological and biochemical characteristics consistent with the enteroendocrine cell phenotype, including the presence of numerous dense core granules and the expression and secretion of chromogranin A and other peptides (e.g. pancreastatin) (10, 12, 13). Thus, the BON cel...

show abstract

Adhesion and migration of cells responding to microtopography

Estévez

Martínez

Yarwood

et al. 2014

J Biomedical Materials Res

View full text Add to dashboard Cite

It is known that cells respond strongly to microtopography. However, cellular mechanisms of response are unclear. Here, we study wild-type fibroblasts responding to 25 µm(2) posts and compare their response to that of FAK(-/-) fibroblasts and fibroblasts with PMA treatment to stimulate protein kinase C (PKC) and the small g-protein Rac. FAK knockout cells modulated adhesion number and size in a similar way to cells on topography; that is, they used more, smaller adhesions, but migration was almost completely stalled demonstrating the importance of FAK signaling in contact guidance and adhesion turnover. Little similarity, however, was observed to PKC stimulated cells and cells on the topography. Interestingly, with PKC stimulation the cell nuclei became highly deformable bringing focus on these surfaces to the study of metastasis. Surfaces that aid the study of cellular migration are important in developing understanding of mechanisms of wound healing and repair in aligned tissues such as ligament and tendon.

show abstract

Interaction of Protein Kinase C Isozymes with Rho GTPases

Cited by 70 publications

References 50 publications

Involvement of vasodilator-stimulated phosphoprotein in UDP-induced microglial actin aggregation via PKC- and Rho-dependent pathways

Involvement of vasodilator-stimulated phosphoprotein in UDP-induced microglial actin aggregation via PKC- and Rho-dependent pathways

The Role of Protein Kinase D in Neurotensin Secretion Mediated by Protein Kinase C-α/-δ and Rho/Rho Kinase

Adhesion and migration of cells responding to microtopography

Contact Info

Product

Resources

About