The C-terminus of PRK2/PKNγ is required for optimal activation by RhoA in a GTP-dependent manner

Lim, Wee Guan; Chen, Xiao; Liu, Junping; Tan, Bee Jen; Zhou, Shu‐Feng; Smith, Audrey; Lees, Nathaniel; Liansheng, Hou; Gu, Fukang; Yu, Xi; Du, Yaomin; Smith, D. J.; Verma, Chandra; Liu, Ke; Duan, Wei

doi:10.1016/j.abb.2008.09.008

Cited by 13 publications

(10 citation statements)

References 46 publications

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“…Quilliam and colleagues [20] found that RhoA binds PKN2 in a GTP dependent manner, but Vincent and Settleman reported that PKN2 binds Rho GDP and Rho GTP with similar kinetics [4]. The extreme C-terminus of PKN2 is also implicated in Rho GTP binding [37], although this specific amino acid sequence seems dispensible for our rescue experiments, since the PKN2/1 chimera will partially rescue. PKN2 and PKN3 contain a proline rich region before the catalytic domain and binding of adaptor proteins known to interact with PKN2 such as Nck or Grb4 has been mapped to this proline rich region [20], [38].…”

Section: Discussionmentioning

confidence: 82%

Regulatory Domain Selectivity in the Cell-Type Specific PKN-Dependence of Cell Migration

et al. 2011

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The mammalian protein kinase N (PKN) family of Serine/Threonine kinases comprises three isoforms, which are targets for Rho family GTPases. Small GTPases are major regulators of the cellular cytoskeleton, generating interest in the role(s) of specific PKN isoforms in processes such as cell migration and invasion. It has been reported that PKN3 is required for prostate tumour cell invasion but not PKN1 or 2. Here we employ a cell model, the 5637 bladder tumour cell line where PKN2 is relatively highly expressed, to assess the potential redundancy of these isoforms in migratory responses. It is established that PKN2 has a critical role in the migration and invasion of these cells. Furthermore, using a PKN wild-type and chimera rescue strategy, it is shown that PKN isoforms are not simply redundant in supporting migration, but appear to be linked through isoform specific regulatory domain properties to selective upstream signals. It is concluded that intervention in PKNs may need to be directed at multiple isoforms to be effective in different cell types.

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Section: Discussionmentioning

confidence: 82%

Regulatory Domain Selectivity in the Cell-Type Specific PKN-Dependence of Cell Migration

et al. 2011

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“…Activated ROCK subsequently phosphorylates a number of substrates, including LIM kinase and myosin light chain phosphatase, and there by modulates actin-myosin cytoskeletal dynamics and contraction [43]. PKN is another serine/threonine kinase that is a direct target of RhoA [39, 44, 45], which has been shown to be activated by LPA in Swiss 3T3 fibroblasts in a Rho-dependent manner [46, 47]. PKN is involved in cytoskeletal regulation, cell adhesion, and cell cycle [48].…”

Section: S1p and Lpa Regulates Rhoa Signaling Through Gα12 /13mentioning

confidence: 99%

Lysophospholipid receptor activation of RhoA and lipid signaling pathways

Xiang¹,

Dusaban²,

Brown³

2013

Biochimica et Biophysica Acta (BBA) - Molecular and Cell Biolog

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The lysophospholipids sphingosine 1-phosphate (S1P) and lysophosphatidic acid (LPA) signal through G-protein coupled receptors (GPCRs) which couple to multiple G-proteins and their effectors. These GPCRs are quite efficacious in coupling to the Gα12/13 family of G-proteins, which stimulate guanine nucleotide exchange factors (GEFs) for RhoA. Activated RhoA subsequently regulates downstream enzymes that transduce signals which affect the actin cytoskeleton, gene expression, cell proliferation and cell survival. Remarkably many of the enzymes regulated downstream of RhoA either use phospholipids as substrates (e.g. phospholipase D, phospholipase C-epsilon, PTEN, PI3 kinase) or are regulated by phospholipid products (e.g. protein kinase D, Akt). Thus lysophospholipids signal from outside of the cell and control phospholipid signaling processes within the cell that they target. Here we review evidence suggesting an integrative role for RhoA in responding to lysophospholipids upregulated in the pathophysiological environment, and in transducing this signal to cellular responses through effects on phospholipid regulatory or phospholipid regulated enzymes.

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“…The PKN family of PKC-related protein kinases constitutes some of the major Rho GTPase-associated protein kinase activities detected in mammalian tissues (Flynn et al, 1998;Lim et al, 2006Lim et al, , 2008Vincent and Settleman, 1997). Although the interaction of PKN1/PKN2 with RhoA and RhoB has been reported, the biological significance of these interactions remains largely unknown.…”

Section: Introductionmentioning

confidence: 99%