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Results for “Adaptor Protein Complex 3”

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PubMed2004

The adaptor protein 3BP2 associates with VAV guanine nucleotide exchange factors to regulate NFAT activation by the B-cell antigen receptor.

Engagement of the B-cell antigen receptor (BCR) activates kinases of the Src and Syk families and signaling complexes assembled by adaptor proteins, which dictate B-cell fate and function. The adaptor 3BP2/SH3BP2, an Abl Src homology domain 3 (SH3)-binding and Syk-kinases interacting protein, exhibits positive regulatory roles in T, natural killer (NK), and basophilic cells. However, its involvement in BCR signaling is completely unknown. Here we show that 3BP2 is tyrosine phosphorylated following BCR aggregation on B lymphoma cells, and that 3BP2 is a substrate for Syk and Fyn, but not Btk. To further explore the function of 3BP2 in B cells, we screened a yeast 2-hybrid B-lymphocyte library and found 3BP2 as a binding partner of Vav proteins. The interaction between 3BP2 and Vav proteins involved both constitutive and inducible mechanisms. 3BP2 also interacted with other components of the BCR signaling pathway, including Syk and phospholipase C gamma (PLC-gamma). Furthermore, overexpression and RNAi blocking experiments showed that 3BP2 regulated BCR-mediated activation of nuclear factor of activated T cells (NFATs). Finally, evidence was provided that 3BP2 functionally cooperates with Vav proteins and Rho GTPases to activate NFATs. Our results show that 3BP2 may regulate BCR-mediated gene activation through Vav proteins.

Adaptor Proteins, Signal Transducing↗

PubMed2006

Atypical polyproline recognition by the CMS N-terminal Src homology 3 domain.

The CIN85/CMS (human homologs of mouse SH3KBP1/CD2AP) family of endocytic adaptor proteins has the ability to engage multiple effectors and couple cargo trafficking with the cytoskeleton. CIN85 and CMS (Cas ligand with multiple Src homology 3 (SH3) domains) facilitate the formation of large multiprotein complexes required for an efficient internalization of cell surface receptors. It has recently been shown that c-Cbl/Cbl-b could mediate the formation of a ternary complex between one c-Cbl/Cbl-b molecule and two SH3 domains of CIN85, important for the ability of Cbl to promote epidermal growth factor receptor down-regulation. To further investigate whether multimerization is conserved within the family of adaptor proteins, we have solved the crystal structures of the CMS N-terminal SH3 domain-forming complexes with Cbl-b- and CD2-derived peptides. Together with biochemical evidence, the structures support the notion that, despite clear differences in the interaction surface, both Cbl-b and CD2 can mediate multimerization of N-terminal CMS SH3 domains. Detailed analyses on the interacting surfaces also provide the basis for a differential Cbl-b molecular recognition of CMS and CIN85.

Adaptor Proteins, Signal Transducing↗

PubMed1998

Association of insulin receptor substrate 3 with SH2 domain-containing proteins in rat adipocytes.

We have recently purified and cloned a new member of the insulin receptor substrate family, designated insulin receptor substrate 3 (IRS-3), from rat adipocytes. The amino acid sequence of IRS-3 shows multiple potential sites for tyrosine phosphorylation in motifs which engage specific SH2 domain-containing proteins. In order to determine which SH2 domain proteins complex with IRS-3, we have searched for coimmunoprecipitation from lysates of untreated and insulin-stimulated adipocytes. Phosphatidylinositol 3-kinase and the tyrosine phosphatase SHP-2 complexed with the tyrosine phosphorylated form of IRS-3, whereas the phospholipase Cgamma did not, and the adaptor Grb2 did so to a much lesser extent. These findings complete the survey of SH2 domain proteins associated with each of the four known members of the IRS family and provide the framework for further analysis of the role of IRS-3 in insulin signaling.

Adaptor Proteins, Signal Transducing↗

PubMed2000

Tyrosine dephosphorylation and deactivation of insulin receptor substrate-1 by protein-tyrosine phosphatase 1B. Possible facilitation by the formation of a ternary complex with the Grb2 adaptor protein.

Regulation of the steady-state tyrosine phosphorylation of the insulin receptor and its postreceptor substrates are essential determinants of insulin signal transduction. However, little is known regarding the molecular interactions that influence the balance of these processes, especially the phosphorylation state of postinsulin receptor substrates, such as insulin receptor substrate-1 (IRS-1). The specific activity of four candidate protein-tyrosine phosphatases (protein-tyrosine phosphatase 1B (PTP1B), SH2 domain-containing PTPase-2 (SHP-2), leukocyte common antigen-related (LAR), and leukocyte antigen-related phosphatase) (LRP) toward IRS-1 dephosphorylation was studied using recombinant proteins in vitro. PTP1B exhibited the highest specific activity (percentage dephosphorylated per microg per min), and the enzyme activities varied over a range of 5.5 x 10(3). When evaluated as a ratio of activity versus IRS-1 to that versus p-nitrophenyl phosphate, PTP1B remained significantly more active by 3.1-293-fold, respectively. Overlay blots with recombinant Src homology 2 domains of IRS-1 adaptor proteins showed that the loss of IRS-1 binding of Crk, GRB2, SHP-2, and the p85 subunit of phosphatidylinositol 3'-kinase paralleled the rate of overall IRS-1 dephosphorylation. Further studies revealed that the adaptor protein GRB2 strongly promoted the formation of a stable protein complex between tyrosine-phosphorylated IRS-1 and catalytically inactive PTP1B, increasing their co-immunoprecipitation from an equimolar solution by 13.5 +/- 3.3-fold (n = 7; p < 0.01). Inclusion of GRB2 in a reaction mixture of IRS-1 and active PTP1B also increased the overall rate of IRS-1 tyrosine dephosphorylation by 2.7-3.9-fold (p < 0.01). These results provide new insight into novel molecular interactions involving PTP1B and GRB2 that may influence the steady-state capacity of IRS-1 to function as a phosphotyrosine scaffold and possibly affect the balance of postreceptor insulin signaling.

Adaptor Proteins, Signal Transducing↗

PubMed1998

Interleukin-2 stimulation induces tyrosine phosphorylation of p120-Cbl and CrkL and formation of multimolecular signaling complexes in T lymphocytes and natural killer cells.

Interleukin (IL)-2, a major growth and differentiation factor for T lymphocytes, was found to induce tyrosine phosphorylation of the proto-oncogene products p120-Cbl and CrkL in IL-2-dependent cell lines. We established that, in unstimulated lymphocytes, the Src homology 2 (SH2) and SH3 domain-containing protein Grb2 and the p85 subunit of phosphatidylinositol 3-kinase, associate constitutively with Cbl via their SH3 domains. Furthermore, IL-2 stimulation increased the level of interaction of phosphorylated Cbl with the p85 SH2 domains, and we provide evidence that the preformed Cbl-Grb2 complex recruits the phosphorylated p52 Shc adaptor protein. In addition, we demonstrate that the SH2-SH3-SH3 adaptor protein CrkL is tyrosine-phosphorylated in an IL-2-dependent manner and, via its SH2 domain, associates with a large proportion of phosphorylated Cbl. We also show that p85 is preassociated with the CrkL SH3 domain. Furthermore, the association of CrkL and p85 is increased after IL-2 treatment by a mechanism involving intermediary tyrosine-phosphorylated proteins that remain to be identified. Our results show that CrkL associates independently with Cbl or p85 and suggest that it also participates in larger complexes containing Cbl and p85. Although the precise roles of Cbl and CrkL remain to be elucidated, their tyrosine phosphorylation, in addition to the multiple protein interactions described here, strongly suggest that Cbl and CrkL may play pivotal roles in the early steps of IL-2 signal transduction.

Adaptor Proteins, Signal Transducing↗

PubMed2001

The actin filament-associated protein AFAP-110 is an adaptor protein that modulates changes in actin filament integrity.

The actin filament-associated protein of 110 kDa (AFAP-110) was first identified as an SH3/SH2 binding partner for the nonreceptor tyrosine kinase, Src. Subsequent data have demonstrated that AFAP-110 can interact with other Src family members. AFAP-110 contains additional protein binding modules including two pleckstrin homology domains, a leucine zipper motif and a target sequence for serine/threonine phosphorylation. AFAP-110 interacts with actin filaments directly via a carboxy terminal actin-binding domain. Thus AFAP-110 may function as an adaptor protein by linking Src family members and/or other signaling proteins to actin filaments. AFAP-110 also has an intrinsic capability to alter actin filament integrity that can be revealed upon conformational changes associated with phosphorylation or mutagenesis. Recent data has indicated that AFAP-110 may also serve to activate cSrc in response to this conformational change as well. Thus, AFAP-110 may function in several ways by (1) acting as an adaptor protein that links signaling molecules to actin filaments, (2) serving as a platform for the construction of larger signaling complexes, (3) serving as an activator of Src family kinases in response to cellular signals that alter its conformation and (4) directly effecting actin filament organization as an actin filament cross-linking protein. Here, we will review the structure and function of AFAP-110 as well as potential binding partners and effectors of AFAP-110's ability to alter actin filament integrity.

Actins↗

PubMed2001

Ski7p G protein interacts with the exosome and the Ski complex for 3'-to-5' mRNA decay in yeast.

Two cytoplasmic mRNA-decay pathways have been characterized in yeast, and both are initiated by shortening of the 3'-poly(A) tail. In the major 5'-to-3' decay pathway, the deadenylation triggers removal of the 5'-cap, exposing the transcript body for 5'-to-3' degradation. An alternative 3'-to-5' decay pathway also follows the deadenylation and requires two multi-complexes: the exosome containing various 3'-exonucleases and the Ski complex consisting of the RNA helicase Ski2p, Ski3p and Ski8p. In addition, Ski7p, which has an N-terminal domain and a C-terminal elongation factor 1alpha-like GTP-binding domain, is involved in the 3'-to-5' decay. However, physical interaction between the exosome and the Ski complex, together with the function of Ski7p, has remained unknown. Here we report that the N domain of Ski7p is required and sufficient for the 3'-to-5' decay. Furthermore, the exosome and the Ski complex interact with the different regions of Ski7p N domain, and both interactions are required for the 3'-to-5' decay. Thus, Ski7p G protein appears to function as a signal-coupling factor between the two multi-complexes operating in the 3'-to-5' mRNA-decay pathway.

Adaptor Proteins, Signal Transducing↗

PubMed2006

Ligation of CD28 stimulates the formation of a multimeric signaling complex involving grb-2-associated binder 2 (gab2), SRC homology phosphatase-2, and phosphatidylinositol 3-kinase: evidence that negative regulation of CD28 signaling requires the gab2 pleckstrin homology domain.

Grb-2-associated binder (Gab)2 is a scaffolding adaptor protein that has been reported to promote growth factor and cytokine receptor signal transduction, but inhibit TCR-mediated signaling events. In this study, we show that ligation of CD28 by its natural ligand B7-1/CD80, induces tyrosine phosphorylation of Gab2 and its coassociation with Src homology phosphatase (SHP)-2 and class IA PI3K in Jurkat cells. Overexpression of wild-type Gab2 revealed a negative role in regulation of CD3/CD28 induction of the transcription factors NF-kappaB and AP-1. To characterize this inhibitory function further, we used Gab2 mutants unable to bind either PI3K or SHP-2 and a PH domain deletion mutant. Although PI3K has previously been implicated as necessary for Gab2-mediated inhibition of TCR signaling, Gab2 mutants defective in their ability to bind PI3K or SHP-2 retained their inhibitory function, whereas deletion of the PH domain ablated the inhibitory effect of Gab2. Together, these data demonstrate that CD28 stimulation of T cells is sufficient to induce an inhibitory multimeric signaling complex involving Gab2, SHP-2, and PI3K. Furthermore, the inhibitory capacity of Gab2 is strictly dependent upon the integrity of its PH domain, suggesting phosphoinositide-mediated membrane recruitment is important to Gab2 function in T cells.

Adaptor Proteins, Signal Transducing↗

PubMed1997

P110delta, a novel phosphoinositide 3-kinase in leukocytes.

Phosphoinositide 3-kinases (PI3Ks) are a family of lipid kinases that have been implicated in signal transduction through tyrosine kinase- and heterotrimeric G-protein-linked receptors. We report herein the cloning and characterization of p110delta, a novel class I PI3K. Like p110alpha and p110beta, other class I PI3Ks, p110delta displays a broad phosphoinositide lipid substrate specificity and interacts with SH2/SH3 domain-containing p85 adaptor proteins and with GTP-bound Ras. In contrast to the widely distributed p110alpha and beta, p110delta is exclusively found in leukocytes. In these cells, p110alpha and delta both associate with the p85alpha and beta adaptor subunits and are similarly recruited to activated signaling complexes after treatment with the cytokines interleukin 3 and 4 and stem cell factor. Thus, these class I PI3Ks appear not to be distinguishable at the level of p85 adaptor selection or recruitment to activated receptor complexes. However, distinct biochemical and structural features of p110delta suggest divergent functional/regulatory capacities for this PI3K. Unlike p110alpha, p110delta does not phosphorylate p85 but instead harbors an intrinsic autophosphorylation capacity. In addition, the p110delta catalytic domain contains unique potential protein-protein interaction modules such as a Pro-rich region and a basic-region leucine-zipper (bZIP)-like domain. Possible selective functions of p110delta in white blood cells are discussed.

Amino Acid Sequence↗

PubMed2004

Specificity of a soluble UDP-galactose: fucoside alpha1,3-galactosyltransferase that modifies the cytoplasmic glycoprotein Skp1 in Dictyostelium.

Skp1 is an adaptor-like protein in E3(SCF)-ubiquitin ligases and other multiprotein complexes of the cytoplasm and nucleus. In Dictyostelium, Skp1 is modified by an unusual pentasaccharide containing a Galalpha1-Fuc linkage, whose formation is examined here. A cytosolic extract from Dictyostelium was found to yield, after 2400-fold purification, an activity that could transfer Gal from UDP-Gal to both a Fuc-terminated glycoform of Skp1 and synthetic Fuc conjugates in the presence of Mn(2+) and dithiothreitol. The microsomal fraction was devoid of activity. The linkage formed was Galalpha1,3Fuc based on co-chromatography with only this synthetic isomer conjugate, and sensitivity to alpha1,3/6-galactosidase. Skp1 exhibited an almost 1000-fold lower K(m) and 35-fold higher V(max) compared with a simple alpha-fucoside, but this advantage was abolished by denaturation or alkylation of Cys residues. A comparison of a complete series of synthetic glycosides representing the non-reducing terminal mono-, di-, and trisaccharides of Skp1 revealed, surprisingly, that the disaccharide is most active owing primarily to a V(max) advantage, but still much less active than Skp1 itself because of a K(m) difference. These findings indicate that alpha-GalT1 is a cytoplasmic enzyme whose modification of Skp1 requires proper presentation of the terminal acceptor disaccharide by a folded Skp1 polypeptide, which correlates with previous evidence that the Galalpha1,3Fuc linkage is deficient in expressed mutant Skp1 proteins.

Animals↗

PubMed1998

Insulin-like growth factor I stimulates tyrosine phosphorylation of p130(Cas), focal adhesion kinase, and paxillin. Role of phosphatidylinositol 3'-kinase and formation of a p130(Cas).Crk complex.

Addition of insulin growth factor-I (IGF-I) to quiescent Swiss 3T3 cells rapidly induced tyrosine phosphorylation of the p130Crk-associated substrate (p130(Cas)), a novel adaptor protein localized at focal adhesions. Half-maximal effect was obtained at 0. 6 nM. IGF-I also promoted the formation of a complex between p130(Cas) and c-Crk and elicited a parallel increase in the tyrosine phosphorylation of p125(Fak) and paxillin. IGF-I-induced p130(Cas), p125(Fak), and paxillin tyrosine phosphorylation could be dissociated from mitogen-activated protein kinase kinase, p70(S6K), and protein kinase C activation. In contrast, the structurally unrelated phosphatidylinositol 3-kinase inhibitors wortmannin and LY294002 markedly attenuated the increase in tyrosine phosphorylation of p130(Cas), p125(Fak), and paxillin induced by IGF-I. Cytochalasin D, which disrupts the network of actin microfilaments, completely prevented tyrosine phosphorylation of p130(Cas), p125(Fak), and paxillin and the formation of a p130(Cas). Crk complex in response to IGF-I. Thus, our results identified a phosphatidylinositol 3-kinase-dependent pathway that requires the integrity of the actin cytoskeleton to induce tyrosine phosphorylation of p130(Cas), p125(Fak), and paxillin in response to IGF-I and suggest that tyrosine phosphorylation of these focal adhesion proteins, together with the recruitment of c-Crk into a complex with p130(Cas), may play a novel role in IGF-I signal transduction.

3T3 Cells↗

PubMed1997

Signaling from the IL-2 receptor to the nucleus.

Interleukin-2 has pleiotropic actions on the immune system and plays a vital role in the modulation of immune responses. Our current understanding of IL-2 signaling has resulted from in vitro studies that have identified the signaling pathways activated by IL-2, including the Jak-STAT pathways, and from in vivo studies that have analyzed mice in which IL-2, each chain of the receptor, as well a number of signaling molecules have been individually targeted by homologous recombination. Moreover, mutations in IL-2Ralpha, gamma(c) and Jak3 have been found in patients with severe combined immunodeficiency. In addition, with the discovery that two components of the receptor, IL-2Rbeta and gamma(c), are shared by other cytokine receptors, we have an enhanced appreciation of the contributions of these molecules towards cytokine specificity, pleiotropy and redundancy.

Adaptor Proteins, Signal Transducing↗

PubMed1993

Structure and function of phosphatidylinositol 3-kinase: a potential second messenger system involved in growth control.

Ligand stimulation of growth factor receptors with intrinsic protein-tyrosine kinase activity initiates the assembly of multienzyme signalling complexes. This is mediated by binding of proteins with src homology 2 (SH2) domains to receptor autophosphorylation sites. Among the proteins involved in complex formation is phosphatidylinositol (PI) 3-kinase, a heterodimeric enzyme composed of 85 kDa and 110 kDa subunits, which binds to receptor (and non-receptor) phosphotyrosine residues through the two SH2 domains in the p85 subunit. p85 acts as an adaptor protein and possibly a regulator of the p110 catalytic subunit that phosphorylates phosphoinositides at the D-3 position of the inositol ring. p85 subunit is composed of several distinct functional domains: one SH3 and two SH2 domains, a p110 binding site and a region with homology to BCR. Expression of these domains in E. coli as GST-fusion proteins has allowed definition by nuclear magnetic resonance (NMR) of three-dimensional structures for the SH2 and SH3 domains. The relationship of structure to function for these domains is discussed. The p110 catalytic domain has a region of homology with vps34p of Saccharomyces cerevisiae, a protein involved in protein sorting to the yeast vacuole. Possible clues to the function of PI 3-kinase derived from this and other observations are presented.

Amino Acid Sequence↗

PubMed1996

Human CLAPS2 encoding AP17, a small chain of the clathrin-associated protein complex: cDNA cloning and chromosomal assignment to 19q13.2-->q13.3.

We have cloned the cDNA for the human homolog of the rat AP17 gene, a small chain of the clathrin-associated protein complex AP-2. The cDNA is highly conserved between rat and human. Human AP17, gene symbol CLAPS2 (clathrin-associated/assembly/adaptor protein, small 3, 17 kDa), was assigned to chromosome region 19q13.2-->q13.3.

Adaptor Protein Complex 2↗

PubMed1997

CSF-1 stimulation induces the formation of a multiprotein complex including CSF-1 receptor, c-Cbl, PI 3-kinase, Crk-II and Grb2.

Recently c-Cbl has been reported to be phosphorylated upon CSF-1 stimulation. The product of the c-cbl proto-oncogene (c-Cbl) is a 120 kDa protein harboring several docking sites for Src homology 2 (SH2) domain containing proteins and proline-rich regions that have been shown to allow its constitutive association with the SH3 domains of Grb2. We demonstrate here that CSF-1 exposure of stable transfectant CHO cells expressing the CSF-1 receptor induced the sustained tyrosine phosphorylation of c-Cbl and its subsequent association with Crk-II and the p85 kDa subunit of the PI 3-kinase, while it constitutively associates with Grb2. We demonstrate by in vitro experiments that these associations require the SH2 domain of Crk-II and both the C- and N-terminal SH2 domains of the p85 subunit of the PI 3-kinase. cCbl is the major PI 3-kinase-containing protein in c-Fms expressing CHO cells upon CSF-1 stimulation. Thus c-Cbl behaves as a core protein, allowing the formation of a quaternary complex including, Crk-II, PI 3-kinase and Grb2. We provide evidence that this multiprotein complex can interact with the tyrosine phosphorylated CSF-1 receptor through the unoccupied SH2 domain of Grb2.

Adaptor Proteins, Signal Transducing↗

PubMed1998

ADP-ribosylation factor 1 transiently activates high-affinity adaptor protein complex AP-1 binding sites on Golgi membranes.

Association of the Golgi-specific adaptor protein complex 1 (AP-1) with the membrane is a prerequisite for clathrin coat assembly on the trans-Golgi network (TGN). The AP-1 adaptor is efficiently recruited from cytosol onto the TGN by myristoylated ADP-ribosylation factor 1 (ARF1) in the presence of the poorly hydrolyzable GTP analog guanosine 5'-O-(3-thiotriphosphate) (GTPgammaS). Substituting GTP for GTPgammaS, however, results in only poor AP-1 binding. Here we show that both AP-1 and clathrin can be recruited efficiently onto the TGN in the presence of GTP when cytosol is supplemented with ARF1. Optimal recruitment occurs at 4 microM ARF1 and with 1 mM GTP. The AP-1 recruited by ARF1.GTP is released from the Golgi membrane by treatment with 1 M Tris-HCl (pH 7) or upon reincubation at 37 degreesC, whereas AP-1 recruited with GTPgammaS or by a constitutively active point mutant, ARF1(Q71L), remains membrane bound after either treatment. An incubation performed with added ARF1, GTP, and AlFn, used to block ARF GTPase-activating protein activity, results in membrane-associated AP-1, which is largely insensitive to Tris extraction. Thus, ARF1. GTP hydrolysis results in lower-affinity binding of AP-1 to the TGN. Using two-stage assays in which ARF1.GTP first primes the Golgi membrane at 37 degreesC, followed by AP-1 binding on ice, we find that the high-affinity nucleating sites generated in the priming stage are rapidly lost. In addition, the AP-1 bound to primed Golgi membranes during a second-stage incubation on ice is fully sensitive to Tris extraction, indicating that the priming stage has passed the ARF1.GTP hydrolysis point. Thus, hydrolysis of ARF1.GTP at the priming sites can occur even before AP-1 binding. Our finding that purified clathrin-coated vesicles contain little ARF1 supports the concept that ARF1 functions in the coat assembly process rather than during the vesicle-uncoating step. We conclude that ARF1 is a limiting factor in the GTP-stimulated recruitment of AP-1 in vitro and that it appears to function in a stoichiometric manner to generate high-affinity AP-1 binding sites that have a relatively short half-life.

ADP-Ribosylation Factor 1↗

PubMed1998

Recent advances in the understanding of interleukin-2 signal transduction.

Interleukin-2 is one of the critical cytokines that control the proliferation and differentiation of cells of the immune system. The present article briefly reviews the current and recently established knowledge on the intracellular signaling events that convert the initial interaction of IL-2 with its receptor into pathways leading to the various biological functions. A first step in IL-2 signaling is the activation of several protein tyrosine kinases that phosphorylate a large array of intracellular substrates including the receptor complex. Phosphorylated tyrosine residues within the receptor then serve as docking sites for multimolecular signaling complexes that initiate three major pathways: the Jak-STAT pathway controlling gene transcription, the Ras-MAPK pathway leading to cell proliferation and gene transcription as well, and the PI3-kinase pathway involved in antiapoptotic signaling and organization of the cytoskeleton. Finally, other recently identified and presumably important tyrosine kinase substrates, whose significance is not yet fully understood, are described.

Adaptor Proteins, Signal Transducing↗

PubMed2002

Regulation of ADL6 activity by its associated molecular network.

Plant dynamin-like proteins consist of a group of high molecular weight GTPase with diverse structural arrangements and cellular localizations. In addition, unlike animal dynamins, there was no evidence for the involvement of any plant dynamin-like protein in clathrin-mediated vesicle trafficking. In this study we demonstrate that ADL6 (Arabidopsis dynamin-like protein 6), due to its domain arrangement, behaves similarly to the animal dynamins. The association of ADL6 with clathrin-coated vesicles was demonstrated by co-fractionation and immunocytochemical studies. ADL6 also interacted via its C-terminus with gamma-adaptin, an adaptor protein of clathrin-coated vesicles. Our results suggest that ADL6 participates in clathrin-mediated vesicle trafficking originating from the Golgi. In addition, our studies demonstrate that ADL6 intrinsic GTPase activity is regulated by its association with acidic phospholipids and an SH3 (Src homology 3)-containing protein.

Adaptor Protein Complex gamma Subunits↗