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Monoclonal Antibody Immunofluorescence Immunocytochemistry Protein Kinase c Binding

$134
20 µl
$336
100 µl
APPLICATIONS
REACTIVITY
Human, Mouse, Rat

Application Methods: Flow Cytometry, Immunofluorescence (Immunocytochemistry), Western Blotting

Background: Myristoylated Alanine-Rich C-Kinase Substrate (MARCKS) is a major PKC substrate expressed in many cell types. MARCKS has been implicated in cell motility, cell adhesion, phagocytosis, membrane traffic, and mitogenesis (1). PKC phosphorylates Ser159, 163, 167, and 170 of MARCKS in response to growth factors and oxidative stress. Phosphorylation at these sites regulates the calcium/calmodulin binding and filamentous (F)-actin cross-linking activities of MARCKS (2-4). Phosphorylation by PKC also results in translocation of MARCKS from the plasma membrane to the cytoplasm (5).

$293
100 µl
APPLICATIONS
REACTIVITY
Human

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

Background: Mitogen- and stress-activated protein kinase 1 (MSK1) and MSK2 are serine/threonine kinases that promote immediate early gene transcription in stress- or mitogen-induced cells (1-4,7, 8) and LPS-stimulated macrophages (9). MSK2, also known as RSKB, contains two catalytic domains and has been shown to interact directly with p38 MAP kinase (10). MSK2 is phosphorylated and activated in response to tumor necrosis factor, epidermal growth factor or phorbol ester in HeLa cells or murine embryonic fibroblasts (MEFs) in a p38- and ERK-dependent manner (8,11). Phosphorylation on residues Ser196 and Thr568 within the activation loop of both catalytic domains is required for full kinase activation (11). Both MSK1 and MSK2 contain a functional nuclear localization sequence that is sufficient and required for nuclear targeting (10). Consistent with their nuclear localization, these kinases play an important role in regulating transcriptional responses to stress and mitogens. Activation of MSK2 in HeLa cells or MEFs results in rapid phosphorylation of histone H3, HMG-14, CREB and ATF1 and acetylation of histone H3 associated with immediate early gene transcription (3,4,6,7).

$122
20 µl
$293
100 µl
APPLICATIONS
REACTIVITY
Human, Monkey

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

Background: Myristoylated Alanine-Rich C-Kinase Substrate (MARCKS) is a major PKC substrate expressed in many cell types. MARCKS has been implicated in cell motility, cell adhesion, phagocytosis, membrane traffic, and mitogenesis (1). PKC phosphorylates Ser159, 163, 167, and 170 of MARCKS in response to growth factors and oxidative stress. Phosphorylation at these sites regulates the calcium/calmodulin binding and filamentous (F)-actin cross-linking activities of MARCKS (2-4). Phosphorylation by PKC also results in translocation of MARCKS from the plasma membrane to the cytoplasm (5).

$134
20 µl
$336
100 µl
APPLICATIONS
REACTIVITY
Human, Mouse

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

Background: Heat shock protein (HSP) 27 is one of the small HSPs that are constitutively expressed at different levels in various cell types and tissues. Like other small HSPs, HSP27 is regulated at both the transcriptional and posttranslational levels (1). In response to stress, the HSP27 expression increases several-fold to confer cellular resistance to the adverse environmental change. HSP27 is phosphorylated at Ser15, Ser78, and Ser82 by MAPKAPK-2 as a result of the activation of the p38 MAP kinase pathway (2,3). Phosphorylation of HSP27 causes a change in its tertiary structure, which shifts from large homotypic multimers to dimers and monomers (4). It has been shown that phosphorylation and increased concentration of HSP27 modulates actin polymerization and reorganization (5,6).

$260
100 µl
APPLICATIONS
REACTIVITY
Human

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

Background: Heat shock protein (HSP) 27 is one of the small HSPs that are constitutively expressed at different levels in various cell types and tissues. Like other small HSPs, HSP27 is regulated at both the transcriptional and posttranslational levels (1). In response to stress, the HSP27 expression increases several-fold to confer cellular resistance to the adverse environmental change. HSP27 is phosphorylated at Ser15, Ser78, and Ser82 by MAPKAPK-2 as a result of the activation of the p38 MAP kinase pathway (2,3). Phosphorylation of HSP27 causes a change in its tertiary structure, which shifts from large homotypic multimers to dimers and monomers (4). It has been shown that phosphorylation and increased concentration of HSP27 modulates actin polymerization and reorganization (5,6).

$111
20 µl
$260
100 µl
APPLICATIONS
REACTIVITY
Human, Monkey

Application Methods: Immunofluorescence (Immunocytochemistry), Immunohistochemistry (Paraffin), Western Blotting

Background: Heat shock protein (HSP) 27 is one of the small HSPs that are constitutively expressed at different levels in various cell types and tissues. Like other small HSPs, HSP27 is regulated at both the transcriptional and posttranslational levels (1). In response to stress, the HSP27 expression increases several-fold to confer cellular resistance to the adverse environmental change. HSP27 is phosphorylated at Ser15, Ser78, and Ser82 by MAPKAPK-2 as a result of the activation of the p38 MAP kinase pathway (2,3). Phosphorylation of HSP27 causes a change in its tertiary structure, which shifts from large homotypic multimers to dimers and monomers (4). It has been shown that phosphorylation and increased concentration of HSP27 modulates actin polymerization and reorganization (5,6).

$122
20 µl
$293
100 µl
APPLICATIONS
REACTIVITY
Human, Monkey, Mouse, Rat

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

Background: The APPL1 multidomain adaptor protein is a BAR-domain protein family member that is involved in membrane trafficking within a number of signal transduction pathways (1). The amino-terminal BAR domain mediates the formation of crescent-shaped APPL1 homodimers (or APPL1 and APPL2 heterodimers) important to lipid binding and membrane curvature sensing (1). The PH domain of APPL1 is required for binding of the adaptor protein to Rab5 GTPase (2). In response to extracellular stimuli, Rab5 GTP hydrolysis releases APPL1 from the endosome and allows translocation of APPL1 to the nucleus where it joins a protein complex that controls chromatin remodeling and gene expression (3). The carboxy-terminal PTB domain of APPL1 enables an interaction between APPL1 and the TrkA neurotrophin receptor. An association between these two proteins and the TrkA-interacting protein GIPC1 within endosomes is required for nerve growth factor mediated signaling (4). APPL1 also binds follicle-stimulating hormone (FSH) receptors, which may provide a relay of FSH signaling to the PI3K/Akt pathway (5). The APPL1 adaptor protein is implicated in insulin signaling, as interaction between APPL1 and Akt2 is required for insulin-stimulated translocation of GLUT4 receptor proteins. Both induced overexpression and knockdown of APPL1 inhibit insulin-stimulated GLUT4 translocation (6). APPL1 binds the adiponectin receptor and acts as a downstream effector in the adiponectin pathway to mediate NO production (7,8). APPL1 interacts with DCC (deleted in colorectal cancer) protein and may play a role in DCC-induced apoptosis (9).

$260
100 µl
APPLICATIONS
REACTIVITY
Human

Application Methods: Immunofluorescence (Immunocytochemistry), Immunoprecipitation

Background: Sequestosome 1 (SQSTM1, p62) is a ubiquitin binding protein involved in cell signaling, oxidative stress, and autophagy (1-4). It was first identified as a protein that binds to the SH2 domain of p56Lck (5) and independently found to interact with PKCζ (6,7). SQSTM1 was subsequently found to interact with ubiquitin, providing a scaffold for several signaling proteins and triggering degradation of proteins through the proteasome or lysosome (8). Interaction between SQSTM1 and TRAF6 leads to the K63-linked polyubiquitination of TRAF6 and subsequent activation of the NF-κB pathway (9). Protein aggregates formed by SQSTM1 can be degraded by the autophagosome (4,10,11). SQSTM1 binds autophagosomal membrane protein LC3/Atg8, bringing SQSTM1-containing protein aggregates to the autophagosome (12). Lysosomal degradation of autophagosomes leads to a decrease in SQSTM1 levels during autophagy; conversely, autophagy inhibitors stabilize SQSTM1 levels. Studies have demonstrated a link between SQSTM1 and oxidative stress. SQSTM1 interacts with KEAP1, which is a cytoplasmic inhibitor of NRF2, a key transcription factor involved in cellular responses to oxidative stress (3). Thus, accumulation of SQSTM1 can lead to an increase in NRF2 activity.

$129
20 µl
$303
100 µl
APPLICATIONS
REACTIVITY
Human, Monkey

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

Background: DNA topoisomerases I and II are nuclear enzymes; type II consists of two highly homologous isoforms: topoisomerase IIα and IIβ. These enzymes regulate the topology of DNA, maintain genomic integrity, and are essential for processes such as DNA replication, recombination, transcription, and chromosome segregation by allowing DNA strands to pass through each other (1). Topoisomerase I nicks and rejoins one strand of the duplex DNA, while topoisomerase II transiently breaks and closes double-stranded DNA (2). Topoisomerases are very susceptible to various stresses. Acidic pH or oxidative stress can convert topoisomerases to DNA-breaking nucleases, causing genomic instability and cell death. DNA-damaging topoisomerase targeting drugs (e.g., etoposide) also convert topoisomerases to nucleases, with the enzyme usually trapped as an intermediate that is covalently bound to the 5+ end of the cleaved DNA strand(s). Research studies have shown that this intermediate leads to genomic instability and cell death. Thus, agents that target topoisomerases are highly sought after cancer chemotherapeutic drugs (3). Ca2+-regulated phosphorylation of topoisomerase IIα at Ser1106 modulates the activity of this enzyme and its sensitivity to targeting drugs (4).

$260
100 µl
APPLICATIONS
REACTIVITY
Human, Monkey

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

Background: Acetylation of the histone tail causes chromatin to adopt an "open" conformation, allowing increased accessibility of transcription factors to DNA. The identification of histone acetyltransferases (HATs) and their large multiprotein complexes has yielded important insights into how these enzymes regulate transcription (1,2). HAT complexes interact with sequence-specific activator proteins to target specific genes. In addition to histones, HATs can acetylate nonhistone proteins, suggesting multiple roles for these enzymes (3). In contrast, histone deacetylation promotes a "closed" chromatin conformation and typically leads to repression of gene activity (4). Mammalian histone deacetylases can be divided into three classes on the basis of their similarity to various yeast deacetylases (5). Class I proteins (HDACs 1, 2, 3, and 8) are related to the yeast Rpd3-like proteins, those in class II (HDACs 4, 5, 6, 7, 9, and 10) are related to yeast Hda1-like proteins, and class III proteins are related to the yeast protein Sir2. Inhibitors of HDAC activity are now being explored as potential therapeutic cancer agents (6,7).

$303
100 µl
APPLICATIONS
REACTIVITY
Human, Mouse

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

Background: Sequestosome 1 (SQSTM1, p62) is a ubiquitin binding protein involved in cell signaling, oxidative stress, and autophagy (1-4). It was first identified as a protein that binds to the SH2 domain of p56Lck (5) and independently found to interact with PKCζ (6,7). SQSTM1 was subsequently found to interact with ubiquitin, providing a scaffold for several signaling proteins and triggering degradation of proteins through the proteasome or lysosome (8). Interaction between SQSTM1 and TRAF6 leads to the K63-linked polyubiquitination of TRAF6 and subsequent activation of the NF-κB pathway (9). Protein aggregates formed by SQSTM1 can be degraded by the autophagosome (4,10,11). SQSTM1 binds autophagosomal membrane protein LC3/Atg8, bringing SQSTM1-containing protein aggregates to the autophagosome (12). Lysosomal degradation of autophagosomes leads to a decrease in SQSTM1 levels during autophagy; conversely, autophagy inhibitors stabilize SQSTM1 levels. Studies have demonstrated a link between SQSTM1 and oxidative stress. SQSTM1 interacts with KEAP1, which is a cytoplasmic inhibitor of NRF2, a key transcription factor involved in cellular responses to oxidative stress (3). Thus, accumulation of SQSTM1 can lead to an increase in NRF2 activity.

$122
20 µl
$303
100 µl
APPLICATIONS
REACTIVITY
Human, Monkey, Mouse, Rat

Application Methods: Immunofluorescence (Immunocytochemistry), Immunohistochemistry (Paraffin), Peptide ELISA (DELFIA), Western Blotting

Background: The ezrin, radixin, and moesin (ERM) proteins function as linkers between the plasma membrane and the actin cytoskeleton and are involved in cell adhesion, membrane ruffling, and microvilli formation (1). ERM proteins undergo intra or intermolecular interaction between their amino- and carboxy-terminal domains, existing as inactive cytosolic monomers or dimers (2). Phosphorylation at a carboxy-terminal threonine residue (Thr567 of ezrin, Thr564 of radixin, Thr558 of moesin) disrupts the amino- and carboxy-terminal association and may play a key role in regulating ERM protein conformation and function (3,4). Phosphorylation at Thr567 of ezrin is required for cytoskeletal rearrangements and oncogene-induced transformation (5). Ezrin is also phosphorylated at tyrosine residues upon growth factor stimulation. Phosphorylation of Tyr353 of ezrin transmits a survival signal during epithelial differentiation (6).

$293
100 µl
APPLICATIONS
REACTIVITY
Human, Monkey, Mouse, Rat

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

Background: JNK-Interacting Proteins (JIPs), as their name implies, coordinate c-Jun N-terminal Kinase (JNK) signaling by acting as scaffolds for components of the JNK signaling cascade (1). JIPs localize and promote JNK activation in response to stress by amalgamating and co-localizing upstream kinases and downstream effectors in the stress-kinase pathway analogous to the mechanism by which AKAPs orchestrate PKA signaling. JIPs bind to an array of MAPKs and other signaling proteins, including the mixed-lineage kinases, MKK7, p38α MAPK, JNK1-3, Max, Myc, NF-κB, LRRK2, and others (1-4).There are four known JIPs, JIP1-4, of which JIP1 and JIP2 share extensive sequence homology and domain structure. JIP1 and JIP2 are mainly expressed in neurons, testis and in β pancreatic cells, where they have been implicated in cellular responses to metabolic stress, the development of diabetes, and post-traumatic brain damage (5-7). Although architecturally distinct from JIP1 and JIP2, JIP3 and JIP4 share some overlapping functions and are more broadly expressed. JIP4, encoded by the SPAG9 (sperm-associated antigen-9) gene, is a homooligomer that binds to and coordinates the activation of numerous components of the stress-activated kinase cascade including MEK4, MEKK3, p38α MAPK, and JNK1-3 (3,8). However, unlike the other JIP members, JIP4 does not appear to activate JNK directly, instead favoring stimulation of p38 MAPK signaling events in response to cellular stress (3,9).In addition to mediating stress responses, JIP4 (or its splice variant, JLP) has also been shown to interact with ARF6 and PIKfyve, thus regulating microtubule-based endosomal trafficking (10,11). There are extensive reports indicating that JIP4 is phosphorylated in response to stress (UV damage etc.) but it is unclear what effect, if any, this has on its function, localization, or binding properties (12-15).

$122
20 µl
$293
100 µl
APPLICATIONS
REACTIVITY
Human, Monkey, Mouse, Rat

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

Background: Ribosomal protein S3 (rpS3) is a component of the 40S ribosomal subunit and is involved in translation. HSP90 interacts with both the amino-terminus and carboxy-terminus of rpS3, preventing its ubiquitination and degradation and thereby retaining the integrity of the ribosome (1). rpS3 has also been shown to function as an endonuclease during DNA damage repair (2,3). Furthermore, overexpression of rpS3 sensitizes lymphocytic cells to cytokine-induced apoptosis, indicating a third role for rpS3 during apoptosis (4). The functions of rpS3 during DNA damage repair and apoptosis have been mapped to two distinct domains (4).

$260
100 µl
APPLICATIONS
REACTIVITY
Mouse, Rat

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

Background: Sequestosome 1 (SQSTM1, p62) is a ubiquitin binding protein involved in cell signaling, oxidative stress, and autophagy (1-4). It was first identified as a protein that binds to the SH2 domain of p56Lck (5) and independently found to interact with PKCζ (6,7). SQSTM1 was subsequently found to interact with ubiquitin, providing a scaffold for several signaling proteins and triggering degradation of proteins through the proteasome or lysosome (8). Interaction between SQSTM1 and TRAF6 leads to the K63-linked polyubiquitination of TRAF6 and subsequent activation of the NF-κB pathway (9). Protein aggregates formed by SQSTM1 can be degraded by the autophagosome (4,10,11). SQSTM1 binds autophagosomal membrane protein LC3/Atg8, bringing SQSTM1-containing protein aggregates to the autophagosome (12). Lysosomal degradation of autophagosomes leads to a decrease in SQSTM1 levels during autophagy; conversely, autophagy inhibitors stabilize SQSTM1 levels. Studies have demonstrated a link between SQSTM1 and oxidative stress. SQSTM1 interacts with KEAP1, which is a cytoplasmic inhibitor of NRF2, a key transcription factor involved in cellular responses to oxidative stress (3). Thus, accumulation of SQSTM1 can lead to an increase in NRF2 activity.

$305
50 tests
100 µl
This Cell Signaling Technology antibody is conjugated to Alexa Fluor® 488 fluorescent dye and tested in-house for direct immunofluorescent analysis in human cells. This antibody is expected to exhibit the same species cross-reactivity as the unconjugated SQSTM1/p62 (D5L7G) Mouse mAb #88588.
APPLICATIONS
REACTIVITY
Human

Application Methods: Immunofluorescence (Immunocytochemistry)

Background: Sequestosome 1 (SQSTM1, p62) is a ubiquitin binding protein involved in cell signaling, oxidative stress, and autophagy (1-4). It was first identified as a protein that binds to the SH2 domain of p56Lck (5) and independently found to interact with PKCζ (6,7). SQSTM1 was subsequently found to interact with ubiquitin, providing a scaffold for several signaling proteins and triggering degradation of proteins through the proteasome or lysosome (8). Interaction between SQSTM1 and TRAF6 leads to the K63-linked polyubiquitination of TRAF6 and subsequent activation of the NF-κB pathway (9). Protein aggregates formed by SQSTM1 can be degraded by the autophagosome (4,10,11). SQSTM1 binds autophagosomal membrane protein LC3/Atg8, bringing SQSTM1-containing protein aggregates to the autophagosome (12). Lysosomal degradation of autophagosomes leads to a decrease in SQSTM1 levels during autophagy; conversely, autophagy inhibitors stabilize SQSTM1 levels. Studies have demonstrated a link between SQSTM1 and oxidative stress. SQSTM1 interacts with KEAP1, which is a cytoplasmic inhibitor of NRF2, a key transcription factor involved in cellular responses to oxidative stress (3). Thus, accumulation of SQSTM1 can lead to an increase in NRF2 activity.

$269
100 µl
APPLICATIONS
REACTIVITY
Human

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

Background: Sequestosome 1 (SQSTM1, p62) is a ubiquitin binding protein involved in cell signaling, oxidative stress, and autophagy (1-4). It was first identified as a protein that binds to the SH2 domain of p56Lck (5) and independently found to interact with PKCζ (6,7). SQSTM1 was subsequently found to interact with ubiquitin, providing a scaffold for several signaling proteins and triggering degradation of proteins through the proteasome or lysosome (8). Interaction between SQSTM1 and TRAF6 leads to the K63-linked polyubiquitination of TRAF6 and subsequent activation of the NF-κB pathway (9). Protein aggregates formed by SQSTM1 can be degraded by the autophagosome (4,10,11). SQSTM1 binds autophagosomal membrane protein LC3/Atg8, bringing SQSTM1-containing protein aggregates to the autophagosome (12). Lysosomal degradation of autophagosomes leads to a decrease in SQSTM1 levels during autophagy; conversely, autophagy inhibitors stabilize SQSTM1 levels. Studies have demonstrated a link between SQSTM1 and oxidative stress. SQSTM1 interacts with KEAP1, which is a cytoplasmic inhibitor of NRF2, a key transcription factor involved in cellular responses to oxidative stress (3). Thus, accumulation of SQSTM1 can lead to an increase in NRF2 activity.

$122
20 µl
$293
100 µl
APPLICATIONS
REACTIVITY
Human, Monkey, Mouse, Rat

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

Background: CDC37 is an important component of the HSP90 chaperone complex (1,2). It was initially identified for its involvement in cell-cycle progression and was later found to have a much broader role as a chaperone for a wide variety of kinases and other proteins (1-3). CDC37 protein has an amino-terminal kinase binding domain followed by a central HSP90 binding domain. It recruits and stabilizes kinases in the HSP90 complex by protecting the newly synthesized kinase peptide chain from degradation and promoting the next step of protein maturation (4,5). CDC37 also suppresses the ATPase activity of HSP90, thereby leading to conformational changes in the complex that preclude target kinase loading (6). CDC37 has been proposed as a therapeutic target because of its important role in multiple kinase pathways involved in proliferation and cancer cell survival, including Raf, Akt, Src, and ErbB2 pathways (7,8).

$293
100 µl
APPLICATIONS
REACTIVITY
Human, Monkey, Mouse, Rat

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

Background: C1QBP, also referred to as p32, p33, gC1q receptor (gC1qR), and hyaluronic acid binding protein 1 (HABP1), was originally identified via its binding interactions with Splicing Factor (SF-2) (1). Multiple, diverse binding partners of C1QBP were subsequently identified, including the globular heads of complement component C1q, hyaluronic acid, selected protein kinases (2), the tumor suppressor ARF (3-5), and multiple antigens of bacterial and viral origin (6). Research studies have shown that C1QBP is overexpressed in a number of cancer cell types (7), and has been implicated in the Warburg effect, whereby cancer cells shift their metabolism from oxidative phosphorylation to glycolysis (7). C1QBP has also been shown to inhibit the Mitochondrial Permeability Transition (MPT) pore, possibly serving a protective function against damage from oxidative stress (8).

$134
20 µl
$336
100 µl
APPLICATIONS
REACTIVITY
Human, Mouse, Rat

Application Methods: Flow Cytometry, Immunofluorescence (Immunocytochemistry), 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).