P J Parker

..There are also distinctions relating to the turnover of these phosphorylations providing a further element of specificity...

..Although this site is crucial to the control of this class of enzymes, the upstream kinase(s) has not been identified...

..This review describes the Sac phosphatase domain-containing proteins and their actions, with particular reference to the genetic and biochemical insights provided by study of the yeast Saccharomyces cerevisiae...

..Furthermore, this in vivo complex is maintained after phosphoinositide 3-kinase inhibition. The control of PRKs by PDK1 thus evidences a novel strategy of substrate-directed control involving GTPases...

..This approach enabled the imaging of PKCalpha activation in live and fixed cultured cells and was also applied to pathological samples...

..1994) J. Biol. Chem. 269, 18299-18302], its phosphorylation is not subject to acute regulation by p42 MAPK in Swiss 3T3 cells...

..It is concluded that SAC1 encodes a novel lipid phosphoinositide phosphatase in which specific mutations can cause the sac1 phenotypes by altering the in vivo regulation of the protein rather than by destroying phosphatase activity...

..The activation loop phosphorylation of PKCdelta in response to serum stimulation of cells was PI 3-kinase-dependent and was enhanced by PDK1 coexpression...

..It is concluded that protein kinase C-delta interacts with GAP-43 through the V0/C2-like domain, outside the catalytic site, and that this interaction is modulated by intracellular Ca2+...

..Translocation of PRK1 to the endosomal compartment by RhoB is accompanied by a shift in the electrophoretic mobility of the kinase indicative of an accompanying activation...

..In the case of the PKCalpha mutant, it was shown that inhibition required the full-length mutant protein. The results provide evidence for the involvement of a common step in the phosphorylation of all PKC isotypes...

..Additionally, it is observed that the V14RhoA mutant binds HR1a but does not bind HR1b. This distinct binding behavior corroborates the conclusion that there are independent contacts on RhoA for the HR1aPRK1 and HR1bPRK1 motifs...

..The mechanisms involved and the implications for signalling studies are discussed...

..The origin and relationships of these predicted proteins is discussed...

..Biochemical data suggest that this domain serves to translocate novel PKC family members to the plasma membrane and may influence binding of PKC activators...

..Deletion of the FAB1 gene produces a loss of vacuolar morphology [6]; it is therefore concluded that PI(3,5)P2, the lipid product of Fab1p, is required for normal vacuolar function...

..The structural similarity between the Schizosaccaromyces pombe Pck proteins and the mammalian Rho-dependent protein kinase C-related family, has led us to investigate the relationship between the function of Rho and that of Pck1/2...

..Thus expression of specific mammalian PKC isotypes up-regulates endocytosis in S. pombe, providing a likely explanation for PKC-mediated receptor internalization in higher eukaryotes...

..The implications for MARCKS as a marker of PKC activation and as a point of signal convergence are discussed...

..These results are discussed in the context of a working model of PKCalpha behavior, providing insight into the workings of other kinases with equivalent sites of phosphorylation...

..It is concluded that the distinct behaviours of PKB and PKC proteins are defined by the typical ground states of these proteins...

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..However, the deletion of the SAC1 domain does not alter PtdInsP3 5-phosphatase activity demonstrating that the SAC1 domain is not necessary for catalytic function...

..In the present paper, the developing understanding of the bi-directional relationship between the protein kinase C family of signal transducers and integrins is discussed...

..p110 alpha) caused this effect. This mode of regulation is discussed in the context of lipid kinase activation in vivo...

..The metabolic map of this pathway and the nature of the binding partner interactions are reviewed...

..The application of this phosphorylation technique should allow the therapeutic potential of targeted 32P to be assessed...

..PRK1 and PRK2, as well as a third member of this family, PRK3, show distinct patterns of expression in adult tissues...

..Material transfer from the cell to the SDM across the membrane tether was monitored by tracking membrane-localized enhanced green fluorescent protein...

..We suggest that there are two possible sites for the phosphorylation of alpha-Gi2; one for C-kinase and the other for an unidentified kinase whose action is triggered by A-kinase activation...

..These data provide a novel negative mechanism for the HGF receptor signaling pathways and highlight a potentially useful target for inhibitors of invasive growth...

..We provide the first evidence that PKCalpha or a PKCalpha-associated serine/threonine kinase can phosphorylate the ERM C-terminal threonine residue within a kinase-ezrin molecular complex in vivo...

..These results suggest that there are multiple sites of interaction between GAP-43 and PKC...

..The ability to acutely and selectively influence compartmental behavior as exemplified here for endomsomes clearly illustrates the power of the approach used to dissect the role of localized signals and events...

..We have recently demonstrated that RhoB binds the RhoA effector, PRK1 and targets it to the endosomal compartment [7]. We show here that RhoB acts through PRK1 to regulate the kinetics of epidermal growth factor receptor traffic...

..Coexpression of this PKC alpha mutant and wild type PKC beta demonstrates that the mutant has a dominant effect upon PKC beta phosphorylation. The location of this region and its phosphorylation in relation to PKC function are discussed...

..There was no dramatic difference in the sequential phosphorylation of MARCKS detectable when comparing the four PKC isotypes. The results are discussed in the context of the functional significance of MARCKS phosphorylation...

..Phosphorylation of GSK-3 beta by PKC results in its specific inactivation. These results are consistent with a model in which activation of PKC stimulates c-Jun DNA binding by inhibiting its phosphorylation by GSK-3 beta...

..PKC beta 1 and beta 2 mRNAs are expressed in a selective manner in both human hematopoietic cells and bovine brain tissues...

..Various PKC pseudosubstrate peptides are phosphorylated by PKC-eta in a phospholipid and TPA-dependent but calcium-independent manner. The polypeptide histone IIIS is a poor substrate...

..These results suggest that PKC-epsilon can regulate a pathway that promotes iNOS expression in macrophages in response to phorbol ester activation...

..Like PKC-epsilon, PKC-delta displays no Ca2+ dependence for activation. The substrate specificity of PCK-delta is similar to that of PKC-epsilon but quite different from other PKCs...

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..Recent evidence indicates that Ras can bind to the p85 alpha/p110 alpha complex. We describe here the functional regulation of the mammalian phosphatidylinositol 3-kinase complex by Ras...

..Furthermore, we demonstrate that in the absence of PKCepsilon, host defense against bacterial infection is severely compromised, resulting in an increased incidence of mortality...

..Both of the major apoptotic cleavage sites of PRK2 in vivo lie within its regulatory domain, suggesting that its activity may be deregulated by proteolysis...

..The corresponding genes are located on distinct human chromosomes; the possibility of even greater genetic complexity of this gene family is suggested by Northern and Southern hybridization analyses...

..Subsequent analysis demonstrated that PKC-epsilon, while showing certain properties characteristic of the PKC family, has a quite distinct substrate specificity and is independent of Ca2+...

..Immune activation of T cells via the protein kinase C pathway thus induces phosphorylation of a single site on the T3 gamma chain, namely serine 126...

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