20% off purchase of 3 or more products* | Learn More >>

Rat Regulation of Signal Transduction

$260
100 µl
APPLICATIONS
REACTIVITY
Human, Mouse, Rat

Application Methods: Western Blotting

Background: Homer1, Homer2 and Homer3 are scaffolding proteins, composed of an EVH protein–binding domain, a coiled-coil domain and a leucine zipper domain. The EVH domain is a protein-protein binding module that binds to the proline-rich motifs PPXXF, PPXF, and LPSSP of G protein–coupled receptors (GPCRs), inositol 1,4,5-triphosphate (IP3) receptors (IP3Rs), ryanodine receptors, and TRP channels (1-2). The coiled-coil and the leucine zipper domains cause multimerization of Homers and assemble signaling proteins complexes. The Homer1 gene encodes a short isoform (Homer1a, aa 1-186) and two long isoforms (Homer1b, aa 1-354; Homer1c, aa 1-366). Homer1a lacks the coiled-coil domain and leucine zipper, antagonizing multimerization of Homers and thus disassembling signaling proteins complexes (3).

$260
100 µl
APPLICATIONS
REACTIVITY
Human, Mouse, Rat

Application Methods: Immunofluorescence (Frozen), Immunoprecipitation, Western Blotting

Background: Contactin-associated protein 1 (Caspr) is a membrane protein that is an essential component of the paranodal junctions in the peripheral and central nervous systems (PNS and CNS, respectively). Caspr is part of the Neurexin family of proteins and is also known as Neurexin IV, Paranodin, and Cntnap1. Caspr forms a complex, via its extracellular domain, with contactin at paranodal junctions of the axon (1, 2). Paranodal junctions are specialized junctions in the axon that are formed between the axolemma and the paranodal loops of myelinating glia. Paranodal structures are critical for salutatory conduction in the PNS and CNS. In the absence of Caspr, Caspr knockout mice exhibit mislocalization of other paranodal junction proteins, including contactin and neurofascin (3). Knockout mice also exhibit reduced nerve conduction velocities, as well as behavior defects consistent with abnormal nerve conduction. Therefore, Caspr is a critical component of a protein complex that is likely central to paranodal junction formation and maintenance.

$260
100 µl
APPLICATIONS
REACTIVITY
Human, Monkey, Mouse, Rat

Application Methods: Immunoprecipitation, Western Blotting

Background: Signal Transducing Adaptor Molecule 1 (STAM1) is a ubiquitously expressed adaptor protein containing an SH3 domain and an ITAM motif. Initial research studies demonstrated that STAM1 undergoes tyrosine phosphorylation following treatment with numerous cytokines and growth factors (1). Subsequent research studies identified STAM1 as a component of the ESCRT-0 complex, which mediates the endocytic sorting of ubiquitinated membrane proteins to the lysosomal compartment for degradation (2). STAM1 harbors a tandemly-oriented VHS (Vps27/Hrs/STAM) domain and UIM (ubiquitin-interacting motif) that facilitates STAM1 binding to ubiquitinated cargo proteins within the endosomal compartment (3,4). Gene targeting studies have revealed that STAM1 and STAM2 cooperate to promote thymic T-cell development and survival (5).

$260
100 µl
APPLICATIONS
REACTIVITY
Human, Mouse, Rat

Application Methods: Immunohistochemistry (Paraffin), Immunoprecipitation, Western Blotting

Background: Epidermal growth factor receptor pathway substrate 8 (Eps8) is an adaptor protein and can be phosphorylated by several receptor tyrosine kinases including EGFR and Src (1,2). Eps8 is composed of an N-terminal PTB domain, followed by an SH3 domain and a C-terminal effector domain. Eps8 controls actin-based motility by capping the barbed end of actin and bundling actin subunits through its C-terminal effector domain (3,4). The C-terminal α hexlical structure of Eps8 interacts directly with actin to exert these capping and bundling functions (5). The actin capping activity requires the release of Eps8 autoinhibitory binding through SH3 domain interaction with an adaptor molecule, such as Abi-1 (6). This SH3 domain of Eps8 also binds to RN-tre to regulate the down stream Rab5-mediated endocytosis pathway (6). Eps8 functions by binding several receptor tyrosine kinases, such as EGFR or FGFR, to enhance receptor mediated mitogenic Rac signaling and Rab5 endocytosis (6,7). The effector region of Eps8 is necessary for this process. By association with Abi-1 and forming the Eps8/Abi-1/Sos-1 complex, Eps8 couples initial growth factor stimulation to actin motility and the Rac activation pathway (8,9). Eps8 has been shown to be important in the cellular function of filopodial protrusions, cell migration, microvilli formation, and focal adhesion (10-13). Research studies have demonstrated that through its involvement in actin related cellular functions, Eps8 plays a role in cancer cell growth, survival, motility, and invasiveness (14-18).

$111
20 µl
$260
100 µl
APPLICATIONS
REACTIVITY
Human, Mouse, Rat

Application Methods: Flow Cytometry, Immunofluorescence (Immunocytochemistry), Immunohistochemistry (Frozen), Immunohistochemistry (Paraffin), Immunoprecipitation, Western Blotting

Background: Survivin is a 16 kDa anti-apoptotic protein highly expressed during fetal development and cancer cell malignancy (1). Survivin binds and inhibits caspase-3, controlling the checkpoint in the G2/M-phase of the cell cycle by inhibiting apoptosis and promoting cell division (2,3). This regulatory process requires the phosphorylation of survivin at Thr34 by p34 cdc2 kinase (4). Gene targeting using a Thr34 phosphorylation-defective survivin mutant, as well as antisense survivin, have been shown to inhibit tumor growth (5,6).

$305
50 tests
100 µl
Cell Signaling Technology antibody is conjugated to Alexa Fluor® 647 fluorescent dye and tested in-house for direct flow cytometric analysis of human cells. The unconjugated antibody, #2808 reacts with survivin from human, mouse, and rat. CST expects that Survivin (71G4E) Rabbit mAb (Alexa Fluor® 647 Conjugate) will also recognize survivin in these species.
APPLICATIONS
REACTIVITY
Human, Mouse, Rat

Application Methods: Flow Cytometry

Background: Survivin is a 16 kDa anti-apoptotic protein highly expressed during fetal development and cancer cell malignancy (1). Survivin binds and inhibits caspase-3, controlling the checkpoint in the G2/M-phase of the cell cycle by inhibiting apoptosis and promoting cell division (2,3). This regulatory process requires the phosphorylation of survivin at Thr34 by p34 cdc2 kinase (4). Gene targeting using a Thr34 phosphorylation-defective survivin mutant, as well as antisense survivin, have been shown to inhibit tumor growth (5,6).

$305
50 tests
100 µl
This Cell Signaling Technology antibody is conjugated to phycoerythrin (PE) and tested in-house for direct flow cytometry analysis in human cells. The antibody is expected to exhibit the same species cross-reactivity as the unconjugated Survivin (71G4B7) Rabbit mAb #2808.
APPLICATIONS
REACTIVITY
Human, Mouse, Rat

Application Methods: Flow Cytometry

Background: Survivin is a 16 kDa anti-apoptotic protein highly expressed during fetal development and cancer cell malignancy (1). Survivin binds and inhibits caspase-3, controlling the checkpoint in the G2/M-phase of the cell cycle by inhibiting apoptosis and promoting cell division (2,3). This regulatory process requires the phosphorylation of survivin at Thr34 by p34 cdc2 kinase (4). Gene targeting using a Thr34 phosphorylation-defective survivin mutant, as well as antisense survivin, have been shown to inhibit tumor growth (5,6).

$305
50 tests
100 µl
This Cell Signaling Technology antibody is conjugated to Alexa Fluor® 488 fluorescent dye and tested in-house for direct flow cytometry and immunofluorescent analysis in human cells.The antibody is expected to exhibit the same species cross-reactivity as the unconjugated Survivin (71G4B7) Rabbit mAb #2808.
APPLICATIONS
REACTIVITY
Human, Mouse, Rat

Application Methods: Flow Cytometry, Immunofluorescence (Immunocytochemistry)

Background: Survivin is a 16 kDa anti-apoptotic protein highly expressed during fetal development and cancer cell malignancy (1). Survivin binds and inhibits caspase-3, controlling the checkpoint in the G2/M-phase of the cell cycle by inhibiting apoptosis and promoting cell division (2,3). This regulatory process requires the phosphorylation of survivin at Thr34 by p34 cdc2 kinase (4). Gene targeting using a Thr34 phosphorylation-defective survivin mutant, as well as antisense survivin, have been shown to inhibit tumor growth (5,6).

$260
100 µl
APPLICATIONS
REACTIVITY
Human, Mouse, Rat

Application Methods: Western Blotting

Background: Chimerins are a family of GTPase-activating proteins (GAPS) that facilitate GTP hydrolysis by the small GTPase Rac, rendering it inactive and regulating cell shape, spreading and motility. Regulation of chimerin proteins occurs in response to growth factor receptor or G-protein coupled receptor activation followed by phospholipase C activation. Chimerins are among the growing number of phorbol ester and diacylglycerol (DAG) effector molecules that do not belong to the PKC family of isoenzymes (reviewed in 1,2). β2-chimerin is highly expressed in brain and pancreas, and its expression is down-regulated in malignant gliomas (3). β2-chimerin is also down-regulated in breast cancer, and its expression causes GAP activity-dependent cell cycle arrest in MCF-7 breast cancer cells (4). Signaling from the epidermal growth factor receptor (EGFR) activates β2-chimerin and allows its association with Rac1 at the plasma membrane (5). Also in response to EGF, diacylglycerol kinase (DGK) γ interacts with β2-chimerin, promotes its translocation to the plasma membrane, and regulate its GAP activity (6).

$260
100 µl
APPLICATIONS
REACTIVITY
Human, Monkey, Mouse, Pig, Rat

Application Methods: Western Blotting

Background: The 14-3-3 family of proteins plays a key regulatory role in signal transduction, checkpoint control, apoptotic and nutrient-sensing pathways (1,2). 14-3-3 proteins are highly conserved and ubiquitously expressed. There are at least seven isoforms, β, γ, ε, σ, ζ, τ, and η that have been identified in mammals. The initially described α and δ isoforms are confirmed to be phosphorylated forms of β and ζ, respectively (3). Through their amino-terminal α helical region, 14-3-3 proteins form homo- or heterodimers that interact with a wide variety of proteins: transcription factors, metabolic enzymes, cytoskeletal proteins, kinases, phosphatases, and other signaling molecules (3,4). The interaction of 14-3-3 proteins with their targets is primarily through a phospho-Ser/Thr motif. However, binding to divergent phospho-Ser/Thr motifs, as well as phosphorylation independent interactions has been observed (4). 14-3-3 binding masks specific sequences of the target protein, and therefore, modulates target protein localization, phosphorylation state, stability, and molecular interactions (1-4). 14-3-3 proteins may also induce target protein conformational changes that modify target protein function (4,5). Distinct temporal and spatial expression patterns of 14-3-3 isoforms have been observed in development and in acute response to extracellular signals and drugs, suggesting that 14-3-3 isoforms may perform different functions despite their sequence similarities (4). Several studies suggest that 14-3-3 isoforms are differentially regulated in cancer and neurological syndromes (2,3).

$260
100 µl
APPLICATIONS
REACTIVITY
Human, Monkey, Mouse, Rat

Application Methods: Western Blotting

Background: Src associated in mitosis 68 kDa (SAM68) is a member of the signal transduction and activation of RNA (STAR) family of RNA binding proteins (1,2). SAM68 is a multi-functional protein with roles in signal transduction, cell cycle regulation, transcription, and alternative splicing (1-3). SAM68 acts as a scaffold protein mediating responses to various stimuli that activate receptors, such as the T-cell receptor and the insulin receptor, linking activation of various signal transduction pathways with post-transcriptional gene regulation (3). SAM68 is a target for phosphorylation by Src-related kinases and Erk1/2 mitogen-activated protein kinases. Phosphorylation of SAM68 regulates both its affinity for RNA and alternative splicing of RNAs like CD44 receptor mRNA (1,4). Many of the activities of SAM68 and its targets for alternative splicing have been implicated in the development and progression of spinal muscular atrophy and cancers such as prostate and breast carcinomas, where SAM68 is frequently upregulated (1,5-8).

$111
20 µl
$260
100 µl
APPLICATIONS
REACTIVITY
Human, Mouse, Rat

Application Methods: Western Blotting

Background: Adiponectin, also termed AdipoQ, Acrp30, apM1 and GBP28, is an adipokine expressed exclusively in brown and white adipocytes (1). It is secreted into the blood and exists in three major forms: a low molecular weight trimer, a medium molecular weight hexamer and a high molecular weight multimer (1). Adiponectin levels are decreased in obese and insulin-resistant mice and humans (2), suggesting that this adipokine is critical to maintain insulin sensitivity. Adiponectin stimulates the phosphorylation of AMPKα at Thr172 and activates AMPK in skeletal muscle (3). It also stimulates glucose uptake in myocytes (3). The block of AMPK activation by a dominant-negative AMPKα2 isoform inhibits the effect of adiponectin on glucose uptake, indicating that adiponectin stimulates glucose uptake and increases insulin sensitivity through its action on AMPK (3). Adiponectin mutants that are not able to form oligomers larger than trimers have no effect on the AMPK pathway (4). Mutations that render adiponectin unable to form high molecular weight multimers are associated with human diabetes (4), indicating the importance of multimerization for adiponectin activity.

$303
100 µl
$717
300 µl
APPLICATIONS
REACTIVITY
Rat

Application Methods: Western Blotting

Background: Protein kinase-like endoplasmic reticulum kinase (PERK) is an eIF2α kinase and transmembrane protein resident in the endoplasmic reticulum (ER) membrane that couples ER stress signals to translation inhibition (1-3). ER stress increases the activity of PERK, which then phosphorylates eIF2α to promote reduced translation. Research studies have demonstrated that PERK-deficient mice have defects in pancreatic β cells several weeks after birth, suggesting a role for PERK-mediated translational control in protecting secretory cells from ER stress (4). PERK activation during ER stress correlates with autophosphorylation of its cytoplasmic kinase domain (1-3). Phosphorylation of PERK at Thr980 serves as a marker for its activation status.

$111
20 µl
$260
100 µl
APPLICATIONS
REACTIVITY
Human, Mouse, Rat

Application Methods: Immunoprecipitation, Western Blotting

Background: The suppressor of cytokine signaling (SOCS) family members are negative regulators of cytokine signal transduction that inhibit the Jak/Stat pathway (1-3). The SOCS family consists of at least 8 members including the originally identified cytokine-inducible SH2-containing protein (CIS1), as well as SOCS1-7. Each SOCS family member contains a central SH2 domain and a conserved carboxy-terminal motif designated as the SOCS box. These proteins are important regulators of cytokine signaling, proliferation, differentiation, and immune responses.

$260
100 µl
APPLICATIONS
REACTIVITY
Human, Mouse, Rat

Application Methods: Immunoprecipitation, Western Blotting

Background: HDAC6 is a class II histone deacetylase enzyme localized to the cytoplasm and associated with the microtubule network (1). It is involved in the regulation of many cellular processes, including cell migration, immune synapse formation, viral infection, and degradation of misfolded proteins (1). HDAC6 contains two tandem catalytic domains that facilitate the deacetylation of multiple protein substrates, including histones and non-histone proteins such as tubulin, cortactin, and HSP90. Despite the ability to deacetylate histone proteins in vitro, there is no evidence for HDAC6-mediated deacetylation of histones in vivo (2,3). The acetylation/deacetylation of tubulin on Lys40 regulates binding and motility of the kinesin-1 motor protein and subsequent transport of cargo proteins such as JNK-interacting protein 1 (JIP1) (4). The acetylation/deacetylation of cortactin regulates cell motility by modulating the binding of cortactin to F-actin (5). Acetylation/deacetylation of HSP90 modulates chaperone complex activity by regulating the binding of an essential cochaperone protein, p23 (6,7). In addition to its role as a protein deacetylase, HDAC6 functions as a component of the aggresome, a proteinaceous inclusion body that forms in response to an accumulation of misfolded or partially denatured proteins (8). Formation of the aggresome is a protective response that sequesters cytotoxic protein aggregates for eventual autophagic clearance from the cell. HDAC6 contains a zinc finger ubiquitin-binding domain that binds both mono- and poly-ubiquitinated proteins (8). HDAC6 binds to both poly-ubiquitinated misfolded proteins and dynein motors, facilitating the transport of misfolded proteins to the aggresome (9,10). HDAC6 is also required for subsequent recruitment of the autophagic machinery and clearance of aggresomes from the cell (11). Thus, HDAC6 plays a key role in the protection against the deleterious effects of pathological protein aggregation that occurs in various diseases, such as neurodegenerative Huntington’s disease (11).

$307
100 µl
APPLICATIONS
REACTIVITY
Human, Mouse, Rat

Application Methods: Immunoprecipitation, Western Blotting

Background: Akt, also referred to as PKB or Rac, plays a critical role in controlling survival and apoptosis (1-3). This protein kinase is activated by insulin and various growth and survival factors to function in a wortmannin-sensitive pathway involving PI3 kinase (2,3). Akt is activated by phospholipid binding and activation loop phosphorylation at Thr308 by PDK1 (4) and by phosphorylation within the carboxy terminus at Ser473. The previously elusive PDK2 responsible for phosphorylation of Akt at Ser473 has been identified as mammalian target of rapamycin (mTOR) in a rapamycin-insensitive complex with rictor and Sin1 (5,6). Akt promotes cell survival by inhibiting apoptosis through phosphorylation and inactivation of several targets, including Bad (7), forkhead transcription factors (8), c-Raf (9), and caspase-9. PTEN phosphatase is a major negative regulator of the PI3 kinase/Akt signaling pathway (10). LY294002 is a specific PI3 kinase inhibitor (11). Another essential Akt function is the regulation of glycogen synthesis through phosphorylation and inactivation of GSK-3α and β (12,13). Akt may also play a role in insulin stimulation of glucose transport (12). In addition to its role in survival and glycogen synthesis, Akt is involved in cell cycle regulation by preventing GSK-3β-mediated phosphorylation and degradation of cyclin D1 (14) and by negatively regulating the cyclin dependent kinase inhibitors p27 Kip1 (15) and p21 Waf1/Cip1 (16). Akt also plays a critical role in cell growth by directly phosphorylating mTOR in a rapamycin-sensitive complex containing raptor (17). More importantly, Akt phosphorylates and inactivates tuberin (TSC2), an inhibitor of mTOR within the mTOR-raptor complex (18,19).

$260
100 µl
APPLICATIONS
REACTIVITY
Bovine, Human, Monkey, Mouse, Pig, Rat

Application Methods: Western Blotting

Background: The 14-3-3 family of proteins plays a key regulatory role in signal transduction, checkpoint control, apoptotic and nutrient-sensing pathways (1,2). 14-3-3 proteins are highly conserved and ubiquitously expressed. There are at least seven isoforms, β, γ, ε, σ, ζ, τ, and η that have been identified in mammals. The initially described α and δ isoforms are confirmed to be phosphorylated forms of β and ζ, respectively (3). Through their amino-terminal α helical region, 14-3-3 proteins form homo- or heterodimers that interact with a wide variety of proteins: transcription factors, metabolic enzymes, cytoskeletal proteins, kinases, phosphatases, and other signaling molecules (3,4). The interaction of 14-3-3 proteins with their targets is primarily through a phospho-Ser/Thr motif. However, binding to divergent phospho-Ser/Thr motifs, as well as phosphorylation independent interactions has been observed (4). 14-3-3 binding masks specific sequences of the target protein, and therefore, modulates target protein localization, phosphorylation state, stability, and molecular interactions (1-4). 14-3-3 proteins may also induce target protein conformational changes that modify target protein function (4,5). Distinct temporal and spatial expression patterns of 14-3-3 isoforms have been observed in development and in acute response to extracellular signals and drugs, suggesting that 14-3-3 isoforms may perform different functions despite their sequence similarities (4). Several studies suggest that 14-3-3 isoforms are differentially regulated in cancer and neurological syndromes (2,3).

$327
50 tests
100 µl
This Cell Signaling Technology antibody is conjugated to Alexa Fluor® 488 fluorescent dye and tested in-house for direct flow cytometric analysis of human cells. The unconjugated Phospho-Akt (Ser473) (193H12) Rabbit mAb #4058 reacts with phospho-Akt (Ser473) from human, mouse and rat. CST expects that Phospho-Akt (Ser473) (193H12) Rabbit mAb (Alexa Fluor® 488 Conjugate) will also recognize phospho-Akt (Ser473) in these species.
APPLICATIONS
REACTIVITY
Human, Mouse, Rat

Application Methods: Flow Cytometry

Background: Akt, also referred to as PKB or Rac, plays a critical role in controlling survival and apoptosis (1-3). This protein kinase is activated by insulin and various growth and survival factors to function in a wortmannin-sensitive pathway involving PI3 kinase (2,3). Akt is activated by phospholipid binding and activation loop phosphorylation at Thr308 by PDK1 (4) and by phosphorylation within the carboxy terminus at Ser473. The previously elusive PDK2 responsible for phosphorylation of Akt at Ser473 has been identified as mammalian target of rapamycin (mTOR) in a rapamycin-insensitive complex with rictor and Sin1 (5,6). Akt promotes cell survival by inhibiting apoptosis through phosphorylation and inactivation of several targets, including Bad (7), forkhead transcription factors (8), c-Raf (9), and caspase-9. PTEN phosphatase is a major negative regulator of the PI3 kinase/Akt signaling pathway (10). LY294002 is a specific PI3 kinase inhibitor (11). Another essential Akt function is the regulation of glycogen synthesis through phosphorylation and inactivation of GSK-3α and β (12,13). Akt may also play a role in insulin stimulation of glucose transport (12). In addition to its role in survival and glycogen synthesis, Akt is involved in cell cycle regulation by preventing GSK-3β-mediated phosphorylation and degradation of cyclin D1 (14) and by negatively regulating the cyclin dependent kinase inhibitors p27 Kip1 (15) and p21 Waf1/Cip1 (16). Akt also plays a critical role in cell growth by directly phosphorylating mTOR in a rapamycin-sensitive complex containing raptor (17). More importantly, Akt phosphorylates and inactivates tuberin (TSC2), an inhibitor of mTOR within the mTOR-raptor complex (18,19).

$305
50 tests
100 µl
This Cell Signaling Technology antibody is conjugated to Alexa Fluor® 647 fluorescent dye and tested in-house for direct flow cytometric analysis of human cells. The unconjugated antibody #2966 reacts with human, mouse, rat and hamster Akt protein. CST expects that Akt (5G3) Mouse mAb (Alexa Fluor® 647 Conjugate) will also recognize Akt in these species.
APPLICATIONS
REACTIVITY
Hamster, Human, Mouse, Rat

Application Methods: Flow Cytometry

Background: Akt, also referred to as PKB or Rac, plays a critical role in controlling survival and apoptosis (1-3). This protein kinase is activated by insulin and various growth and survival factors to function in a wortmannin-sensitive pathway involving PI3 kinase (2,3). Akt is activated by phospholipid binding and activation loop phosphorylation at Thr308 by PDK1 (4) and by phosphorylation within the carboxy terminus at Ser473. The previously elusive PDK2 responsible for phosphorylation of Akt at Ser473 has been identified as mammalian target of rapamycin (mTOR) in a rapamycin-insensitive complex with rictor and Sin1 (5,6). Akt promotes cell survival by inhibiting apoptosis through phosphorylation and inactivation of several targets, including Bad (7), forkhead transcription factors (8), c-Raf (9), and caspase-9. PTEN phosphatase is a major negative regulator of the PI3 kinase/Akt signaling pathway (10). LY294002 is a specific PI3 kinase inhibitor (11). Another essential Akt function is the regulation of glycogen synthesis through phosphorylation and inactivation of GSK-3α and β (12,13). Akt may also play a role in insulin stimulation of glucose transport (12). In addition to its role in survival and glycogen synthesis, Akt is involved in cell cycle regulation by preventing GSK-3β-mediated phosphorylation and degradation of cyclin D1 (14) and by negatively regulating the cyclin dependent kinase inhibitors p27 Kip1 (15) and p21 Waf1/Cip1 (16). Akt also plays a critical role in cell growth by directly phosphorylating mTOR in a rapamycin-sensitive complex containing raptor (17). More importantly, Akt phosphorylates and inactivates tuberin (TSC2), an inhibitor of mTOR within the mTOR-raptor complex (18,19).

$260
100 µl
APPLICATIONS
REACTIVITY
Human, Monkey, Mouse, Rat

Application Methods: Immunoprecipitation, Western Blotting

Background: Akt, also referred to as PKB or Rac, plays a critical role in controlling survival and apoptosis (1-3). This protein kinase is activated by insulin and various growth and survival factors to function in a wortmannin-sensitive pathway involving PI3 kinase (2,3). Akt is activated by phospholipid binding and activation loop phosphorylation at Thr308 by PDK1 (4) and by phosphorylation within the carboxy terminus at Ser473. The previously elusive PDK2 responsible for phosphorylation of Akt at Ser473 has been identified as mammalian target of rapamycin (mTOR) in a rapamycin-insensitive complex with rictor and Sin1 (5,6). Akt promotes cell survival by inhibiting apoptosis through phosphorylation and inactivation of several targets, including Bad (7), forkhead transcription factors (8), c-Raf (9), and caspase-9. PTEN phosphatase is a major negative regulator of the PI3 kinase/Akt signaling pathway (10). LY294002 is a specific PI3 kinase inhibitor (11). Another essential Akt function is the regulation of glycogen synthesis through phosphorylation and inactivation of GSK-3α and β (12,13). Akt may also play a role in insulin stimulation of glucose transport (12). In addition to its role in survival and glycogen synthesis, Akt is involved in cell cycle regulation by preventing GSK-3β-mediated phosphorylation and degradation of cyclin D1 (14) and by negatively regulating the cyclin dependent kinase inhibitors p27 Kip1 (15) and p21 Waf1/Cip1 (16). Akt also plays a critical role in cell growth by directly phosphorylating mTOR in a rapamycin-sensitive complex containing raptor (17). More importantly, Akt phosphorylates and inactivates tuberin (TSC2), an inhibitor of mTOR within the mTOR-raptor complex (18,19).