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Human Regulation of Gtpase Activity

$303
100 µl
APPLICATIONS
REACTIVITY
Human

Application Methods: Western Blotting

Background: In multicellular organisms, intercellular junctions play essential roles in tissue integrity and maintenance of cell polarity. Tight junctions (TJs) form a continuous barrier to fluids across the epithelium and endothelium (reviewed in 1). Adherens junctions (AJs) are dynamic structures that form cell-cell contacts linking cells into a continuous sheet (reviewed in 2). The actin filament-binding protein, Afadin, binds to nectin forming a connection to the actin cytoskeleton (3). AJs are formed when nectin assembles cadherin at the cell-cell adhesion site and these junctions are then involved in the formation and maintenance of TJs (4,5). Afadin has two splice variants: l-afadin, which is ubiquitously expressed, and s-afadin, which is expressed predominantly in neural tissue. s-Afadin is a shorter form lacking one of the three proline-rich regions found in l-afadin, as well as the carboxyl-terminal F-actin binding region (6). Human s-afadin is identical to AF-6, the ALL-1 fusion partner involved in acute myeloid leukemias (7). Recent work has also shown that afadin is involved in controlling the directionality of cell movement when it is localized at the leading edge of moving cells (8,9).

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

Application Methods: Immunoprecipitation, Western Blotting

Background: In multicellular organisms, intercellular junctions play essential roles in tissue integrity and maintenance of cell polarity. Tight junctions (TJs) form a continuous barrier to fluids across the epithelium and endothelium (reviewed in 1). Adherens junctions (AJs) are dynamic structures that form cell-cell contacts linking cells into a continuous sheet (reviewed in 2). The actin filament-binding protein, Afadin, binds to nectin forming a connection to the actin cytoskeleton (3). AJs are formed when nectin assembles cadherin at the cell-cell adhesion site and these junctions are then involved in the formation and maintenance of TJs (4,5). Afadin has two splice variants: l-afadin, which is ubiquitously expressed, and s-afadin, which is expressed predominantly in neural tissue. s-Afadin is a shorter form lacking one of the three proline-rich regions found in l-afadin, as well as the carboxyl-terminal F-actin binding region (6). Human s-afadin is identical to AF-6, the ALL-1 fusion partner involved in acute myeloid leukemias (7). Recent work has also shown that afadin is involved in controlling the directionality of cell movement when it is localized at the leading edge of moving cells (8,9).

$260
100 µl
APPLICATIONS
REACTIVITY
Human

Application Methods: Western Blotting

Background: IQGAPs are scaffolding proteins involved in mediating cytoskeletal function. They contain multiple protein interaction domains and bind to a growing number of molecules including actin, myosin light chain, calmodulin, E-cadherin, and β-catenin (reviewed in 1). Through their GAP-related domains, they bind the small GTPases Rac1 and cdc42. IQGAPs lack GAP activity, however, and regulate small GTPases by stabilizing their GTP-bound (active) forms (2,3). Research studies have shown that the function and distribution of the IQGAP proteins widely vary. IQGAP1 is ubiquitously expressed and has been found to interact with APC (4) and the CLIP170 complex (5) in response to small GTPases, promoting cell polarization and migration. Additional research studies have suggested that IQGAP1 could play a part in the invasiveness of some cancers (6-8). IQGAP2, which is about 60% identical to IQGAP1, is expressed primarily in liver (3), but lower levels have been detected in the prostate, kidney, thyroid, stomach, and testis (9,10). Research studies have shown that IQGAP2 displays tumor suppressor properties (11). Less is known about the function of IQGAP3, but this protein is present in the lung, brain, small intestine, and testis (9) and is only expressed in proliferating cells (12), suggesting a role in cell growth and division.

$303
100 µl
APPLICATIONS
REACTIVITY
Human, Monkey, Mouse

Application Methods: Immunoprecipitation, Western Blotting

Background: ARHGAP family members activate Rho GTPase proteins (1). Mutations of ARHGAP family genes lead to carcinogenesis through the dysregulation of Rho/Rac/Cdc42-like GTPases (2). Little is known about the biological function of ARHGAP42, a member of the ARHGAP family. ARHGAP42 contains a RhoGAP domain in the middle of its sequence, an SH3 binding domain at the C-terminal end of the protein sequence, as well as a BAR domain and a PH domain in the N-terminal region of the sequence, which indicate that the protein may function as GTPase activator and cytoskeletal adaptor.

$260
100 µl
APPLICATIONS
REACTIVITY
Human, Mouse, Rat

Application Methods: Immunoprecipitation, Western Blotting

Background: DOCK180 and its partner, ELMO1, interact directly with one another to form an atypical two-part guanine nucleotide exchange factor (GEF) for the small GTPase Rac (1). Rac activation occurs in association with p130 Cas and Crk, which form a complex with DOCK180 that is targeted to focal adhesions (2,3). DOCK180 is also recruited to the plasma membrane by binding to phosphoinositides (4). ELMO1 may function as an inhibitor of proteasome-dependent degradation of DOCK180 at the plasma membrane to regulate reorganization of the actin cytoskeleton (5). Localized Rac activation allows actin nucleation via WAVE family proteins, signaling to integrins, formation of lamellipodia and filopodia, and regulation of processes such as phagocytosis and cell migration (6-8).

$260
100 µl
APPLICATIONS
REACTIVITY
Human, Mouse, Rat

Application Methods: Western Blotting

Background: The MCF2/Dbl proto-oncogene product is the founding member of the Dbl family of Rho guanine nucleotide exchange factors (GEFs) that are characterized by their Dbl homology (DH) domain (1). GEFs stimulate the formation of the active, GTP-bound form of small GTPases such as Rho, Rac and Cdc42, signaling to various downstream molecules and regulating diverse cell functions. While the overexpressed, full-length Dbl gene has transforming activity (2), mutations resulting in truncated Dbl cause the protein to become highly oncogenic. This truncated form of Dbl, which lacks the amino-terminal 497 amino acids, has constitutive GEF activity (3) and is more stable than the full-length variant (4), allowing for increased signaling to downstream effector molecules.Dbl interacts with ezrin, a member of the ezrin/radixin/moesin (ERM) family of proteins that links the plasma membrane to the actin cytoskeleton. Dbl interacts with ezrin in lipid microdomains, which leads to Cdc42 activation and the regulation of processes such as filopodia formation and cell polarity (5,6). Dbl localization and biological activities are regulated in part by phosphatidylinositol 3-kinase (PI3K) (7). Dbl is also involved in cell survival and inhibits apoptosis through induction of Akt phosphorylation at Thr308 (8).

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

Application Methods: Western Blotting

Background: The Rho family of small GTPases, including Rho, Rac, and Cdc42, act as molecular switches that regulate processes such as cell migration, adhesion, proliferation, and differentiation. They are activated by guanine nucleotide exchange factors (GEFs), which catalyze the exchange of bound GDP for GTP, and inhibited by GTPase activating proteins (GAPs), which catalyze the hydrolysis of GTP to GDP (1). The serine- and proline-rich GAP protein, Cdc42 GAP (CdGAP), has been shown to be a negative regulator of both Cdc42 and Rac1, but not RhoA (2,3). This protein contains three domains: an amino-terminal GAP domain, a central domain, and a carboxy-terminal proline-rich domain containing five Src homology 3 (SH3)-binding sites. It is suggested that threonine and serine phosphorylation within the proline-rich domain likely alters protein-protein interactions and determines the localization of CdGAP (4). Phosphorylation of CdGAP on threonine 776 by both ERK-1 and GSK-3 has been shown to negatively regulate protein activity, possibly by inducing a conformational change within the protein disrupting its ability to bind SH3 domains (4,5). Upregulation of CdGAP has been shown to increase cell proliferation and it has been suggested that this protein may play a role in TGF-β-induced cell growth, motility, and invasion in some breast cancer cells (6).

$260
100 µl
APPLICATIONS
REACTIVITY
Human

Application Methods: Immunoprecipitation, Western Blotting

Background: BCAR3 is a member of the novel SH2-containing protein (NSP) family (1). It was identified as a gene product involved in anti-estrogen resistance in the context of breast cancer (2). Like other members of this family, BCAR3 has been shown to interact with the family member, CAS. The C terminal Cdc25 homolgy domain of BCAR3 interacts tightly with the FAT domain of p130Cas (3) and promotes the association of p130cas with Src kinase (4) to activate related signaling pathways. Overexpression of BCAR3 leads to the activation of a wide range of downstream signaling proteins including PI3K, rac, PAK1, and cyclin D1 (5-7). The main role of BCAR3 is to promote cell motility and regulate cytoskeletal remodeling and adhesion through its effect on p130cas and Src kinase (8-10). BCAR3 also has been implicated in playing an inhibitory role on TGF-β/SMAD signaling, which is associated with favorable disease outcomes (11).

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

Application Methods: Immunoprecipitation, Western Blotting

Background: Ran GTPase activating protein 1 (RanGAP1) regulates GTP hydrolysis by Ran, which is required for the ability of Ran to regulate nucleocytoplasmic shuttling (1). A significant fraction of cellular RanGAP1 is covalently modified by SUMO-1, which is required for relocalization of RanGAP1from the cytoplasm to the nuclear pore complex and the mitotic spindle (2-5). Research studies demonstrate that RanGAP1 sumoylation is required for stable association of RanGAP1 with RanBP2. Together with the SUMO-conjugating enzyme UBC9/UBE2I, RanGAP1 and RanBP2 are part of a SUMO E3 ligase complex that is implicated in regulating nucleocytoplasmic protein trafficking (6-8). Phosphorylation of RanGAP1 occurs in a cell-cycle-dependent manner and may play a role in regulating RanGAP1 catalytic activity (9,10).

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

Application Methods: Immunoprecipitation, Western Blotting

Background: OCRL1 is an inositol 5-phosphatase that selectively dephosphorylates the 5 position of the inositol ring. Its substrates include phosphatidylinositol 4,5-bisphosphate, inositol 1,4,5-trisphosphate, and inositol 1,3,4,5-tetrakisphosphate (1). Research studies indicate that mutations in OCRL1 are linked to Oculocerebrorenal syndrome or Lowe syndrome, an X-linked disorder distinguished by mental retardation and congenital cataracts, as well as Dent's disease (2,3). OCRL1 interacts with several endocytic proteins, including clathrin, AP-2, and RabGTPases (4-7). OCRL1 is localized to the Golgi complex, endosomes, and late stage clathrin-coated pits (6,8). OCRL1 controls early endosome function (8), regulating membrane traffic from endosomes to the Golgi. It is also involved in cytokinesis (9) and cilia assembly (10).

$260
100 µl
APPLICATIONS
REACTIVITY
Human

Application Methods: Immunoprecipitation, Western Blotting

Background: ADP-ribosylation factor GTPase activating protein 1 (ARFGAP1) is a Golgi-localized protein that regulates vesicle formation and membrane trafficking (1). ARFGAP1 initiates cargo selection and COP1 vesicle formation by stimulating GTP hydrolysis of ADP-ribosylation factor ARF1 (2). This GTPase activating protein initiates vesicle transport by coupling vesicle formation with cargo sorting (3). ARFGAP1 plays an active role in the Golgi-to-ER retrograde, intra-Golgi, and trans-Golgi trafficking networks (1). Research studies indicate that ARFGAP1 can act as a GTPase activating protein for LRRK2, a large multifunction protein whose genetic mutations are associated with Parkinson’s disease (4). ARFGAP1 regulates GTPase activity and promotes the kinase activity of LRRK2, which suggests some potential as a promising target for study of LRRK2 mediated neurodegeneration (4).

$260
100 µl
APPLICATIONS
REACTIVITY
Human, Mouse, Rat

Application Methods: Immunoprecipitation, Western Blotting

Background: ADP-ribosylation factor GTPase activating protein 1 (ARFGAP1) is a Golgi-localized protein that regulates vesicle formation and membrane trafficking (1). ARFGAP1 initiates cargo selection and COP1 vesicle formation by stimulating GTP hydrolysis of ADP-ribosylation factor ARF1 (2). This GTPase activating protein initiates vesicle transport by coupling vesicle formation with cargo sorting (3). ARFGAP1 plays an active role in the Golgi-to-ER retrograde, intra-Golgi, and trans-Golgi trafficking networks (1). Research studies indicate that ARFGAP1 can act as a GTPase activating protein for LRRK2, a large multifunction protein whose genetic mutations are associated with Parkinson’s disease (4). ARFGAP1 regulates GTPase activity and promotes the kinase activity of LRRK2, which suggests some potential as a promising target for study of LRRK2 mediated neurodegeneration (4).

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

Application Methods: Western Blotting

Background: The RalA binding protein 1 (RalBP1 or RLIP76) was originally identified as a GTP-RalA associated protein that acted as a downstream RalA effector in regulating Ral-Ras signaling (1). RalBP1 interacts with RalA and the endocytosis protein REPS2 (POB1) through its carboxy-terminal Ral binding domain. RalBP1 has an intrinsic GTPase activating function and interacts with Cdc42 through its centrally located Rho-GAP domain (1-3). A protein complex containing RalBP1/POB1/RalA regulates endocytosis of membrane receptors (4). RalBP1 also functions as a non-ABC transporter that catalyzes the ATP-dependent transport of numerous xenobiotics, including glutathione conjugates and some chemotherapeutic agents. RalBP1 transporter activity may play an important role in detoxification, drug resistance and the stress response (5-7). Increased expression of RalBP1 protein is associated with some forms of cancer and regression of cancer xenografts results from RalBP1 inhibition (8,9). Evidence to date suggests that RalBP1 may be a promising therapeutic target for cancer therapy.

$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

Application Methods: Immunoprecipitation, Western Blotting

Background: The RalA binding protein 1 (RalBP1 or RLIP76) was originally identified as a GTP-RalA associated protein that acted as a downstream RalA effector in regulating Ral-Ras signaling (1). RalBP1 interacts with RalA and the endocytosis protein REPS2 (POB1) through its carboxy-terminal Ral binding domain. RalBP1 has an intrinsic GTPase activating function and interacts with Cdc42 through its centrally located Rho-GAP domain (1-3). A protein complex containing RalBP1/POB1/RalA regulates endocytosis of membrane receptors (4). RalBP1 also functions as a non-ABC transporter that catalyzes the ATP-dependent transport of numerous xenobiotics, including glutathione conjugates and some chemotherapeutic agents. RalBP1 transporter activity may play an important role in detoxification, drug resistance and the stress response (5-7). Increased expression of RalBP1 protein is associated with some forms of cancer and regression of cancer xenografts results from RalBP1 inhibition (8,9). Evidence to date suggests that RalBP1 may be a promising therapeutic target for cancer therapy.

$260
100 µl
APPLICATIONS
REACTIVITY
Human, Monkey

Application Methods: Western Blotting

Background: G protein-coupled receptor (GPCR) kinase interacting proteins 1 and 2 (GIT1 and GIT2) are highly conserved, ubiquitous scaffold proteins involved in localized signaling to help regulate focal contact assembly and cytoskeletal dynamics. GIT proteins contain multiple interaction domains that allow interaction with small GTPases (including ARF, Rac, and cdc42), kinases (such as PAK and MEK), the Rho family GEF Pix, and the focal adhesion protein paxillin (reviewed in 1). GIT1 and GIT2 share many of the same properties, but with at least ten distinct, tissue-specific splice variants. GIT2 has been shown to play an important role inhibiting focal adhesion turnover and membrane protrusion (2,3). Focal adhesion localization and paxillin binding of GIT2 is regulated through phosphorylation at one or more tyrosine sites (Tyr286, Tyr392, Tyr592) by FAK and/or Src (4,5,reviewed in 6). Once at the focal adhesion, GIT2 is thought to play a key role in cell polarity and migration, making it a protein of interest in the investigation of oncogenic signaling pathways (3,5,7).

$260
100 µl
APPLICATIONS
REACTIVITY
Human, Monkey, Mouse

Application Methods: Western Blotting

Background: G protein-coupled receptor (GPCR) kinase interacting proteins 1 and 2 (GIT1 and GIT2) are highly conserved, ubiquitous scaffold proteins involved in localized signaling to help regulate focal contact assembly and cytoskeletal dynamics. GIT proteins contain multiple interaction domains that allow interaction with small GTPases (including ARF, Rac, and cdc42), kinases (such as PAK and MEK), the Rho family GEF Pix, and the focal adhesion protein paxillin (reviewed in 1). GIT1 and GIT2 share many of the same properties, but with at least ten distinct, tissue-specific splice variants. GIT2 has been shown to play an important role inhibiting focal adhesion turnover and membrane protrusion (2,3). Focal adhesion localization and paxillin binding of GIT2 is regulated through phosphorylation at one or more tyrosine sites (Tyr286, Tyr392, Tyr592) by FAK and/or Src (4,5,reviewed in 6). Once at the focal adhesion, GIT2 is thought to play a key role in cell polarity and migration, making it a protein of interest in the investigation of oncogenic signaling pathways (3,5,7).

$260
100 µl
APPLICATIONS
REACTIVITY
Human

Application Methods: Western Blotting

Background: RanBP1 is a Ran binding protein that functions in nuclear trafficking for both nuclear import and export (1-3). Its protein sequence contains a Ran binding domain and a C-terminal nuclear export signal, which maintains its cytoplasmic localization (2,3). During nuclear export, RanBP1 forms a complex with RanGTP and CRM1/cargo, leading to dissociation of cargo from CRM1 (2,4). RanBP1 further stimulates RanGTP-RanGAP1 association to facilitate RanGTP hydrolysis and the generation of RanGDP to complete the final steps of nuclear export (5). During nuclear import, RanBP1 stabilizes the formation of a RanGDP-importin/NLS receptor-RanBP1 complex. This complex regulates the release of imported cargo into the nucleus (6,7). In addition to nuclear trafficking, RanBP1 also controls RanGTP distribution along mitotic microtubules, which localizes critical factors, such as cyclin B1 and HURP, to mitotic microtubles and regulates chromosome segregation (8,9). In vivo knock down or overexpression of RanBP1 has been shown to affect cellular ciliogenesis by regulating the local RanGTP concentation at the base of cilia (10).

$260
100 µl
APPLICATIONS
REACTIVITY
Human, Mouse, Rat

Application Methods: Western Blotting

Background: GTPase Regulator Associated with Focal Adhesion Kinase-1 (GRAF1), is a GTPase-activating protein for the small G proteins RhoA and Cdc42 (1). It is composed of an N-terminal BAR domain, a PH domain, a RhoGAP domain, a proline-rich domain, and a C-terminal SH3 domain. GRAF1 contributes to the clathrin-independent carriers/GPI-enriched early endosomal compartments (CLIC/GEEC) pathway, and was the first specific protein component of this endocytic pathway to be discovered (2). GRAF1 was identified as an important protein necessary for adeno-associated virus 2 infection (3). In addition, research studies have linked GRAF1 to mental retardation (4), skeletal muscle differentiation (5), and myeloid leukemia (6,7).

$303
100 µl
APPLICATIONS
REACTIVITY
Human

Application Methods: Western Blotting

Background: G protein-coupled receptor (GPCR) kinase interacting proteins 1 and 2 (GIT1 and GIT2) are highly conserved, ubiquitous scaffold proteins involved in localized signaling to help regulate focal contact assembly and cytoskeletal dynamics. GIT proteins contain multiple interaction domains that allow interaction with small GTPases (including ARF, Rac, and cdc42), kinases (such as PAK and MEK), the Rho family GEF Pix, and the focal adhesion protein paxillin (reviewed in 1). GIT1 and GIT2 share many of the same properties, but with at least ten distinct, tissue-specific splice variants. GIT2 has been shown to play an important role inhibiting focal adhesion turnover and membrane protrusion (2,3). Focal adhesion localization and paxillin binding of GIT2 is regulated through phosphorylation at one or more tyrosine sites (Tyr286, Tyr392, Tyr592) by FAK and/or Src (4,5,reviewed in 6). Once at the focal adhesion, GIT2 is thought to play a key role in cell polarity and migration, making it a protein of interest in the investigation of oncogenic signaling pathways (3,5,7).