Objective: The transcription factor NF-κB and the MAP kinases JNK1/2 are known to play decisive roles in cytokine-induced damage of rodent β-cells. The upstream events by which these factors are activated in response to cytokines are, however, uncharacterized. The aim of the present investigation was to elucidate a putative role of the MAP kinase kinase kinase-1 (MEKK-1) in cytokine-induced signaling.. Research Design and Methods: To establish a functional role of MEKK-1, the effects of transient MEKK-1 overexpression in βTC-6 cells, achieved by lipofection and cell sorting, and MEKK-1 downregulation in βTC-6 cells and human islet cells, achieved by diced-siRNA treatment, were studied.. Results: We observed that overexpression of wild type MEKK-1, but not of a kinase dead MEKK-1 mutant, resulted in potentiation of cytokine-induced JNK activation, IκB degradation, NF-κB translocation and cell death. Downregulation of MEKK-1 in human islet cell provoked opposite effects, i.e. attenuation of ...
The protein encoded by this gene is a serine/threonine kinase and is part of some signal transduction cascades, including the ERK and JNK kinase pathways as well as the NF-kappa-B pathway. The encoded protein is activated by autophosphorylation and requires magnesium as a cofactor in phosphorylating other proteins. This protein has E3 ligase activity conferred by a plant homeodomain (PHD) in its N-terminus and phospho-kinase activity conferred by a kinase domain in its C-terminus. [provided by RefSeq, Mar 2012 ...
View mouse Map3k15 ChrX:159988433-160123351 with: phenotypes, sequences, polymorphisms, proteins, references, function, expression
p>The checksum is a form of redundancy check that is calculated from the sequence. It is useful for tracking sequence updates.,/p> ,p>It should be noted that while, in theory, two different sequences could have the same checksum value, the likelihood that this would happen is extremely low.,/p> ,p>However UniProtKB may contain entries with identical sequences in case of multiple genes (paralogs).,/p> ,p>The checksum is computed as the sequence 64-bit Cyclic Redundancy Check value (CRC64) using the generator polynomial: x,sup>64,/sup> + x,sup>4,/sup> + x,sup>3,/sup> + x + 1. The algorithm is described in the ISO 3309 standard. ,/p> ,p class="publication">Press W.H., Flannery B.P., Teukolsky S.A. and Vetterling W.T.,br /> ,strong>Cyclic redundancy and other checksums,/strong>,br /> ,a href="http://www.nrbook.com/b/bookcpdf.php">Numerical recipes in C 2nd ed., pp896-902, Cambridge University Press (1993),/a>),/p> Checksum:i ...
The reverse-genetic analysis of MAP kinase signaling that we report in this study began with the identification of a deletion mutation affecting the tandemly duplicated genes MEKK1, MEKK2, and MEKK3. This mekk1/2/3 allele was isolated by screening ∼2000 progeny of a selfed mekk1(+/−) mekk3(+/−) trans-heterozygote to search for rare recombinants that brought the mekk1 and mekk3 T-DNA alleles into the cis configuration. The apparent genotype of the individual that we isolated from this screen was mekk1(+/−) mekk3(−/−). Upon further PCR analysis, however, we determined that this line appeared to be carrying a deletion that encompassed the entire MEKK1, MEKK2, MEKK3 gene family. The first clue that a deletion was present in this line came from our observation that the T-DNA border junctions present on the inside flanks of the mekk1 and mekk3 T-DNA loci were absent in mekk1/2/3 homozygous plants. Follow-up analysis indicated that the MEKK2 gene was also absent in these plants. The exact ...
The PDB archive contains information about experimentally-determined structures of proteins, nucleic acids, and complex assemblies. As a member of the wwPDB, the RCSB PDB curates and annotates PDB data according to agreed upon standards. The RCSB PDB also provides a variety of tools and resources. Users can perform simple and advanced searches based on annotations relating to sequence, structure and function. These molecules are visualized, downloaded, and analyzed by users who range from students to specialized scientists.
MEKK3 is a conserved Ser/Thr protein kinase belonging to the MAPK kinase kinase (MAP3K) family. MEKK3 is constitutively expressed in T cells, but its function in T cell immunity has not been fully elucidated. Using Mekk3 T cell conditional knockout (T-cKO) mice, we show that MEKK3 is required for T cell immunity in vivo. Mekk3 T-cKO mice had reduced T cell response to bacterial infection and were defective in clearing bacterial infections. The Ag-induced cytokine production, especially IFN-γ production, was impaired in Mekk3-deficient CD4 T cells. The TCR-induced ERK1/2, JNK, and p38 MAPKs activation was also defective in Mekk3-deficient CD4 T cells. In vitro, MEKK3 is not required for Th1 and Th2 cell differentiation. Notably, under a nonpolarizing condition (Th0), Mekk3 deficiency led to a significant reduction of IFN-γ production in CD4 T cells. Furthermore, the IL-12/IL-18-driven IFN-γ production and MAPK activation in Mekk3-deficient T cells was not affected suggesting that MEKK3 may selectively
Homo sapiens mitogen-activated protein kinase kinase kinase 4 (MAP3K4), transcript variant 1, mRNA. (H00004216-R06) - Products - Abnova
Homo sapiens mitogen-activated protein kinase kinase kinase 7 (MAP3K7), transcript variant A, mRNA. (H00006885-R01V) - Products - Abnova
Gene target information for MAP3K20 - mitogen-activated protein kinase kinase kinase 20 (human). Find diseases associated with this biological target and compounds tested against it in bioassay experiments.
ASK1 (phospho Ser966) antibody (mitogen-activated protein kinase kinase kinase 5) for IHC-P, WB. Anti-ASK1 (phospho Ser966) pAb (GTX50229) is tested in Human, Mouse samples. 100% Ab-Assurance.
TABLE-US-00001 TABLE 1 Oligo Accession Gene ID Number Number number Gene Name Symbol APOB-10167- 12138 NM_000384 Apolipoprotein B (including Ag(x) antigen) APOB 20-12138 APOB-10167- 12139 NM_000384 Apolipoprotein B (including Ag(x) antigen) APOB 20-12139 MAP4K4-2931- 12266 NM_004834 Mitogen-Activated Protein Kinase Kinase Kinase Kinase 4 MAP4K4 13-12266 (MAP4K4), transcript variant 1 MAP4K4-2931- 12293 NM_004834 Mitogen-Activated Protein Kinase Kinase Kinase Kinase 4 MAP4K4 16-12293 (MAP4K4), transcript variant 1 MAP4K4-2931- 12383 NM_004834 Mitogen-Activated Protein Kinase Kinase Kinase Kinase 4 MAP4K4 16-12383 (MAP4K4), transcript variant 1 MAP4K4-2931- 12384 NM_004834 Mitogen-Activated Protein Kinase Kinase Kinase Kinase 4 MAP4K4 16-12384 (MAP4K4), transcript variant 1 MAP4K4-2931- 12385 NM_004834 Mitogen-Activated Protein Kinase Kinase Kinase Kinase 4 MAP4K4 16-12385 (MAP4K4), transcript variant 1 MAP4K4-2931- 12386 NM_004834 Mitogen-Activated Protein Kinase Kinase Kinase Kinase 4 MAP4K4 ...
May be involved in an oxidative stress-mediated signaling cascade that phosphorylates downstream MAP kinases MPK3 and MPK6. May suppress auxin signaling that promotes cell cycle. Functionally redundant to ANP2 and ANP3 in the positive regulation of cytokinesis.
Exhibits JUN kinase kinase kinase activity. Involved in positive regulation of nervous system development and protein phosphorylation. Predicted to localize to the membrane. Is expressed in diencephalon lateral wall mantle layer; dorsal grey horn; late tubule; midbrain mantle layer; and ureter. Orthologous to human MAP3K13 (mitogen-activated protein kinase kinase kinase 13 ...
Cell microarrays are a promising tool for performing large-scale functional genomic screening in mammalian cells at reasonable cost, but owing to technical limitations they have been restricted for use with a narrow range of cell lines and short-term assays. Here, we describe MicroSCALE (Microarrays of Spatially Confined Adhesive Lentiviral Features), a cell microarray-based platform that enables application of this technology to a wide range of cell types and longer-term assays. We used MicroSCALE to uncover kinases that when overexpressed partially desensitized B-RAFV600E-mutant melanoma cells to inhibitors of the mitogen-activated protein kinase kinase kinase (MAPKKK) RAF, the MAPKKs MEK1 and 2 (MEK1/2, mitogen-activated protein kinase kinase 1 and 2), mTOR (mammalian target of rapamycin), or PI3K (phosphatidylinositol 3-kinase). These screens indicated that cells treated with inhibitors acting through common mechanisms were affected by a similar profile of overexpressed proteins. In ...
Transforming growth factor-β (TGF-β) signals through its receptor, composed of the type I and type II subunits (TβRI and TβRII), to stimulate a pathway involving Smads, as well as Smad-independent signaling. Sorrentino et al. found that in cells transfected with TAK1 [TGF-β-associated kinase 1, a member of the mitogen-activated protein kinase kinase kinase (MAPKKK) family that is upstream of p38 and ubiquitin], TGF-β1 stimulated the ubiquitylation of TAK1, as well as the phosphorylation of TAK1, which is an indication of activation. When a mutant form of ubiquitin that could not form Lys63-linked chains was transfected into the cells, TAK1 ubiquitylation and phosphorylation, recruitment of TAB2 (TAK-associated binding protein 2), and activation of p38 was diminished. Pharmacological inhibition of TβRI kinase activity failed to block TGF-β-stimulated TAK1 and p38 activation but did block Smad activation, suggesting that activation of the p38 MAPK pathway was independent of the kinase ...
This gene product is a 626-amino acid polypeptide that is 96.5% identical to mouse Mekk3. Its catalytic domain is closely related to those of several other kinases, including mouse Mekk2, tobacco NPK, and yeast Ste11. Northern blot analysis revealed a 4.6-kb transcript that appears to be ubiquitously expressed. This protein directly regulates the stress-activated protein kinase (SAPK) and extracellular signal-regulated protein kinase (ERK) pathways by activating SEK and MEK1/2 respectively; it does not regulate the p38 pathway. In cotransfection assays, it enhanced transcription from a nuclear factor kappa-B (NFKB)-dependent reporter gene, consistent with a role in the SAPK pathway. Alternatively spliced transcript variants encoding distinct isoforms have been observed. [provided by RefSeq, Jul 2008 ...
Map3k3 - Lenti ORF clone of Map3k3 (mGFP-tagged) - Mouse mitogen-activated protein kinase kinase kinase 3 (Map3k3) available for purchase from OriGene - Your Gene Company.
Sensing the osmolarity of the environment is a critical response for all organisms. Whereas bacteria will migrate away from high osmotic conditions, most eukaryotic cells are not motile and use adaptive metabolic responses for survival. The p38 MAPK pathway is a crucial mediator of survival during cellular stress. We have discovered a novel scaffold protein that binds to actin, the GTPase Rac, and the upstream kinases MEKK3 and MKK3 in the p38 MAPK phospho-relay module. RNA interference (RNAi) demonstrates that MEKK3 and the scaffold protein are required for p38 activation in response to sorbitol-induced hyperosmolarity. FRET identifies a cytoplasmic complex of the MEKK3 scaffold protein that is recruited to dynamic actin structures in response to sorbitol treatment. Through its ability to bind actin, relocalize to Rac-containing membrane ruffles and its obligate requirement for p38 activation in response to sorbitol, we have termed this protein osmosensing scaffold for MEKK3 (OSM). The Rac-OSM-MEKK3
The observation that MEKK1 can be proteolyzed to very specific fragments prompted us to determine whether p35 or CrmA could inhibit the generation of fragments A, B, C, and D. Figure 6A shows that p35 almost totally and CrmA partially inhibited the appearance of fragments B and C. Quantitation of the fragments in six independent experiments revealed that CrmA and p35, while leaving the relative proportion of fragment A unchanged, diminished the relative proportion of fragment B by 50 and 90%, respectively. This result indicates that these protease inhibitors prevented the formation of fragments B and C but had no effect on the proteolytic activity that cleaves MEKK1 into fragment A. Since the cleavage of MEKK1 into fragment A was unaffected by CrmA and p35, it was surprising to find that the amount of fragment D, the corresponding moiety of fragment A, was reduced in the presence of the inhibitors (Fig. 6A, right panel). However, since fragment D could be derived from fragment C, blocking the ...
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TY - JOUR. T1 - Ssk2 mitogen-activated protein kinase kinase kinase governs divergent patterns of the stress-activated Hog1 signaling pathway in Cryptococcus neoformans. AU - Bahn, Yong Sun. AU - Geunes-Boyer, Scarlett. AU - Heitman, Joseph. PY - 2007/12. Y1 - 2007/12. N2 - The stress-activated p38/Hog1 mitogen-activated protein kinase (MAPK) pathway is structurally conserved in many diverse organisms, including fungi and mammals, and modulates myriad cellular functions. The Hog1 pathway is uniquely specialized to control differentiation and virulence factors in a majority of clinical Cryptococcus neoformans serotype A and D strains. Here, we identified and characterized the Ssk2 MAPKKK that functions upstream of the MAPKK Pbs2 and the MAPK Hog1 in C. neoformans. The SSK2 gene was identified as a potential component responsible for the difference in Hog1 phosphorylation between the serotype D f1 sibling strains B-3501 and B-3502 through comparative analysis of meiotic maps showing their meiotic ...
The mitogen-activated protein kinase kinase (MEK) kinase 1 (MEKK1) mediates activin B signals required for eyelid epithelium morphogenesis during mouse fetal development. The present study investigates the role of MEKK1 in epithelial wound healing, another activin-regulated biological process. In a skin wound model, injury markedly stimulates MEKK1 expression and activity, which are in turn required for the expression of genes involved in extracellular matrix (ECM) homeostasis. MEKK1 ablation or down-regulation by interfering RNA significantly delays skin wound closure and impairs activation of Jun NH2-terminal kinases, induction of plasminogen activator inhibitor (PAI)-1, and restoration of cell-cell junctions of the wounded epidermis. Conversely, expression of wild-type MEKK1 accelerates reepithelialization of full-thickness skin and corneal debridement wounds by mechanisms involving epithelial cell migration, a cell function that is partially abolished by neutralizing antibodies for PAI-1 and
Background: Alzheimers Disease (AD) is a neuron related brain disorder leading to reasoning and memory loss. There is no specific cure identified for AD. JNK3 (c-Jun N-terminal kinase /stress-activated protein kinase) are highly revealed within the central nervous system, particularly neurons, playing vital role in functioning of brain. JNK3 hyper phosphorylation is a very common conclusion in neurodegenerative diseases. JNK3 in turn hyper phosphorylates Amyloid Precursor Protein (APP) which leads to the formation of Amyloid β peptides (an inductive agent of Alzheimers disease). Methods: Protein JNK-3 (PDB ID: 3KVX) was retrieved from protein data bank and later we docked a library of compounds against it. These were further validated by ADMET studies. Results: Thus, docking inhibitors of JNK3 may provide a promising sanitive approach. Based on best docking score and glide score a potential lead is identified against JNK3. Conclusion: Inhibiting JNK-3 may lead to less production of amyloidβ ...
TY - JOUR. T1 - Signal transduction pathways regulated by mitogen-activated/extracellular response kinase kinase kinase induce cell death. AU - Johnson, Nancy Lassignal. AU - Gardner, Anne M.. AU - Diener, Katrina M.. AU - Lange-Carter, Carol A.. AU - Gleavy, Janice. AU - Jarpe, Matthew B.. AU - Minden, Audrey. AU - Karin, Michael. AU - Zon, Leonard I.. AU - Johnson, Gary L.. PY - 1996/2/9. Y1 - 1996/2/9. N2 - Mitogen-activated/extracellular response kinase kinase (MEK) kinase (MEKK) is a serine-threonine kinase that regulates sequential protein phosphorylation pathways, leading to the activation of mitogen-activated protein kinases (MAPK), including members of the Jun kinase (JNK)/stress- activated protein kinase (SAPK) family. In Swiss 3T3 and REF52 fibroblasts, activated MEKK induces cell death involving cytoplasmic shrinkage, nuclear condensation, and DNA fragmentation characteristic of apoptosis. Expression of activated MEKK enhanced the apoptotic response to ultraviolet irradiation, ...
The Raf-1 protein, encoded by the c-raf-1 gene, is a 75 kDa serine-threonine kinase that functions as a key regulator of cell growth, proliferation, and survival (1) . Raf-1 is a critical component of multiple signal transduction pathways, integrating signals from cell membrane-bound growth factor receptors and apoptotic regulators (2) . Activated Raf-1 in turn interfaces with a many downstream targets controlling proliferation and survival, including activation of the mitogen-activated protein kinase/extracellular signal-regulated kinase kinases MEK1 and MEK2, activation of the nuclear factor κB survival and proliferation pathway, and inhibition of the proapoptotic factor Bad (3) .. Deregulated Raf-1 activity has been implicated in oncogenic transformation (4 , 5) . Constitutive Raf-1 activation leads to morphological changes consistent with a malignant phenotype, to growth factor-independent proliferation, and to increased resistance to cytotoxic agents (6) . Raf-1 promotes full malignant ...
The HER-2 oncogene, a member of the erythroblastosis oncogene B (ERBB)-like oncogene family, has been shown to be amplified in many types of cancer, including breast cancer. However, the molecular mechanism of HER-2 overexpression is not completely understood. The phosphorylation of proteins on the serine or threonine residues that immediately precede proline (pSer/Thr-Pro) is specifically catalyzed by the prolyl isomerase Pin1 and is a key signaling mechanism in cell proliferation and transformation. Here, we found that Pin1 interacts with mitogen-activated protein kinase/extracellular signal-regulated kinase kinase (MEK) protein kinase 1, resulting in the induction of HER-2 expression. Pin1−/− mouse embryonic fibroblasts exhibited a decrease in epidermal growth factor (EGF)-induced MEK1/2 phosphorylation compared with Pin1+/+ mouse embryonic fibroblast. In addition, a knockdown of Pin1 resulted in the inhibition of MEK1/2 phosphorylation induced by EGF in MCF-7 cells. Furthermore, PD98059, ...
Looking for online definition of MEKK11 in the Medical Dictionary? MEKK11 explanation free. What is MEKK11? Meaning of MEKK11 medical term. What does MEKK11 mean?
Kaga S, Ragg S, Rogers KA, Ochi A. Activation of p21-CDC42/Rac-activated kinases by CD28 signaling: p21-activated kinase (PAK) and MEK kinase 1 (MEKK1) may mediate the interplay between CD3 and CD28 signals. J Immunol. 1998 May 01; 160(9):4182-9 ...
Pontus Jäntti Sulkapallokoulu, Ristihaantie 2, Espoo (2020) - Pontus Jäntti Sulkapallokoulu järjestää valmennusta sekä lapsille et
nited States Patent 3,532,543 BATTERY EMPLOYING LITHIUM-SUL- PHUR ELECTRODES WITH NON-AQUE- OUS ELECTROLYTE Dominick A. Nole, Sacramento, and Vladimir Moss, Rancho Cordova, Calif., assignors to Aerojet-General Corporation, El Monte, Calif., a corporation of Ohio No Drawing. Filed Feb. 21, 1968, Ser. No. 707,330 Int. Cl. H01m 35/02, 39/04 US. Cl. 1366 1 Claim ABSTRACT OF THE DISCLOSURE A battery utilizing a non-aqueous electrolyte employing a solvent such as ethylene carbonate, propylene carbonate, dimethoxyethane and y-butyrolactone and mixtures thereof and a lithium salt solute and containing the reaction product of carbon disulfide and finely divided lithium powder, a lithium anode and a sulphur-containing cathode. This invention relates to electric cells and, more particularly, provides a battery utilizing a non-aqueous electrolyte, and electrodes of lithium and sulphur. Lithium batteries have been investigated heretofore, some of which are operable at ambient temperatures and others at ...
We have previously reported the in vitro pharmacological properties of E6201, including the following: 1) E6201 suppressed the activation of AP-1 via inhibitory effects on mitogen-activated protein kinase/extracellular signal-regulated kinase kinase-1 and mitogen-activated protein kinase/extracellular signal-regulated kinase kinase kinase-; 2) E6201 decreased activation of NF-κB; 3) E6201 suppressed the production of various proinflammatory cytokines in human monocytes and leukocytes; and 4) E6201 attenuated hyperproliferation and IL-8 production in human keratinocytes in vitro (Goto et al., 2009). These pharmacological properties of E6201 indicate that this compound represents a promising strategy for the treatment of psoriasis, because psoriasis is a chronic inflammatory skin disease characterized by severe hyperplasia in the epidermis and marked infiltration of leukocytes into dermis and epidermis. In this article, we investigated the therapeutic effects of topically administered E6201 in ...
Catalytic domain of the Protein Serine/Threonine Kinases, Mitogen-Activated Protein Kinase Kinase Kinase Kinase 4 and 6. Serine/threonine kinases (STKs), mitogen-activated protein kinase (MAPK) kinase kinase kinase 4 (MAPKKKK4 or MAP4K4) and MAPKKKK6 (or MAP4K6) subfamily, catalytic (c) domain. STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. The MAP4K4/MAP4K6 subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase. Members of this subfamily contain an N-terminal catalytic domain and a C-terminal citron homology (CNH) regulatory domain. MAP4Ks (or MAPKKKKs) are involved in MAPK signaling pathways that are important in mediating cellular responses to extracellular signals by activating a MAPK kinase kinase (MAPKKK or MAP3K or MKKK). Each MAPK cascade is activated ...
Featured Publications. Development of small molecules targeting the pseudokinase Her3. Lim SM, Xie T, Westover KD, Ficarro SB, Tae HS, Gurbani D, Sim T, Marto JA, Jänne PA, Crews CM, Gray NS Bioorg. Med. Chem. Lett. 2015 May Neutrophil-lymphocyte and platelet-lymphocyte ratios as prognostic factors following stereotactic radiation therapy for early-stage non-small cell lung cancer. Cannon NA, Meyer J, Iyengar P, Ahn C, Westover KD, Choy H, Timmerman R J Thorac Oncol 2014 Oct Discovery of Type II Inhibitors of TGFß-Activated Kinase 1 (TAK1) and Mitogen-Activated Protein Kinase Kinase Kinase Kinase 2 (MAP4K2). Tan L, Nomanbhoy T, Gurbani D, Patricelli M, Hunter J, Geng J, Herhaus L, Zhang J, Pauls E, Ham Y, Choi HG, Xie T, Deng X, Buhrlage SJ, Sim T, Cohen P, Sapkota G, Westover KD, Gray NS J. Med. Chem. 2014 Jul In situ selectivity profiling and crystal structure of SML-8-73-1, an active site inhibitor of oncogenic K-Ras G12C. Hunter JC, Gurbani D, Ficarro SB, Carrasco MA, Lim SM, Choi HG, Xie ...
Söderström T.S., Poukkula M., Holmström T.H., et al. Mitogen-activated protein kinase/extracellular signal-regulated kinase signaling in activated T cells abrogates TRAIL-induced apoptosis upstream of the mitochondrial amplification loop and caspase-8. (англ.) // J. Immunol. (англ.)русск. : journal. - 2002. - Vol. 169, no. 6. - P. 2851-2860. - PMID 12218097. ...
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Mary Schmeida, PhD, RN Citation: Schmeida, M., (October 10, 2005). "Legislative: Health Insurance Portability and Accountability Act of 1996: Just an Incremental Step in Reshaping Government." OJIN: The Online Journal of Issues in Nursing. Vol. 11, No 1.. DOI: 10.3912/OJIN.Vol11No01LegCol01. Introduction to HIPAA. In 1996, the federal Health Insurance Portability and Accountability Act (HIPAA) was adopted as a step toward reshaping government health care. Referred to as the HIPAA, it enables portability of health care insurance coverage for workers and their families when they change or lose their jobs (Title I), sets a standard or benchmark for safeguarding electronic and paper exchange of health information, and requires national identifiers for providers, health plans, and employers (Title II). The final policy implementation rule outlines the entities affected by the legislation as health care providers, health plans, health care clearinghouses, and vendors offering computer software ...