myopic: Biological Overview | References
Gene name - myopic
Cytological map position - 70F4-70F5
Function - signaling protein
Keywords - Hippo/Warts pathway, regulation of receptor endocytosis, integrin trafficking, controls Yorkie endosomal association and protein levels, tumor suppressor Egfr pathway, Toll pathway - immune reponse, wing, eye
Symbol - mop
FlyBase ID: FBgn0036448
Genetic map position - chr3L:14762441-14769229
Cellular location - cytoplasmic
Pradhan-Sundd, T. and Verheyen, E. M. (2015). The Myopic-Ubpy-Hrs nexus enables endosomal recycling of Frizzled. Mol Biol Cell [Epub ahead of print]. PubMed ID: 26224310
Endosomal trafficking of signaling proteins plays an essential role in cellular homeostasis. The seven-pass transmembrane protein, Frizzled (Fz) is a critical component of the Wnt signaling. Although Wnt signaling is proposed to be regulated by endosomal trafficking of Fz, the molecular events that enable this regulation are not completely understood. This study shows that the endosomal protein Myopic (Mop) regulates Fz trafficking in the Drosophila wing disk by inhibiting the ubiquitination and degradation of Hrs. Deletion of Mop or Hrs results in endosomal accumulation of Fz and therefore reduced Wnt signaling. The in situ Proximity Ligation Assay revealed a strong association between Mop and Hrs in the Drosophila wing disk. Overexpression of Hrs rescues the trafficking defect caused by mop knockdown. Mop aids in the maintenance of Ubpy which deubiquitinates (and thus stabilizes) Hrs. In the absence of the ubiquitin ligase Cbl, Mop is dispensable. These findings support a previously unknown role for Mop in endosomal trafficking of Fz in Wnt-receiving cells.
|Loncle, N., Agromayor, M., Martin-Serrano, J. and Williams, D. W. (2015). An ESCRT module is required for neuron pruning. Sci Rep 5: 8461. PubMed ID: 25676218
Neural circuits are refined by both functional and structural changes. Structural remodeling by large-scale pruning occurs where relatively long neuronal branches are cut away from their parent neuron and removed by local degeneration. Until now, the molecular mechanisms executing such branch severing events have remained poorly understood. This study reveal a role for the Endosomal Sorting Complex Required for Transport (ESCRT) machinery during neuronal remodeling. The data show that a specific ESCRT pruning module, including members of the ESCRT-I and ESCRT-III complexes, but not ESCRT-0 or ESCRT-II, are required for the neurite scission event during pruning. Furthermore it was shown that this ESCRT module requires a direct, in vivo, interaction between Shrub/CHMP4B and the accessory protein Myopic/HD-PTP.
|Bulgari, D., Jha, A., Deitcher, D. L. and Levitan, E. S. (2018). Myopic (HD-PTP, PTPN23) selectively regulates synaptic neuropeptide release. Proc Natl Acad Sci U S A [Epub ahead of print]. PubMed ID: 29378961
Neurotransmission is mediated by synaptic exocytosis of neuropeptide-containing dense-core vesicles (DCVs) and small-molecule transmitter-containing small synaptic vesicles (SSVs). Exocytosis of both vesicle types depends on Ca(2+) and shared secretory proteins. This study shows that increasing or decreasing expression of Myopic (mop, HD-PTP, PTPN23), a Bro1 domain-containing pseudophosphatase implicated in neuronal development and neuropeptide gene expression, increases synaptic neuropeptide stores at the Drosophila neuromuscular junction (NMJ). This occurs without altering DCV content or transport, but synaptic DCV number and age are increased. The effect on synaptic neuropeptide stores is accounted for by inhibition of activity-induced Ca(2+)-dependent neuropeptide release. cAMP-evoked Ca(2+)-independent synaptic neuropeptide release also requires optimal Myopic expression, showing that Myopic affects the DCV secretory machinery shared by cAMP and Ca(2+) pathways. Presynaptic Myopic is abundant at early endosomes, but interaction with the endosomal sorting complex required for transport III (ESCRT III) protein (CHMP4/Shrub) that mediates Myopic's effect on neuron pruning is not required for control of neuropeptide release. Remarkably, in contrast to the effect on DCVs, Myopic does not affect release from SSVs. Therefore, Myopic selectively regulates synaptic DCV exocytosis that mediates peptidergic transmission at the NMJ.
Protein tyrosine phosphatases (PTPs) are a group of tightly regulated enzymes that coordinate with protein tyrosine kinases to control protein phosphorylation during various cellular processes. Using genetic analysis in Drosophila non-transmembrane PTPs, one role was identified that Myopic (Mop), the Drosophila homolog of the human His domain phosphotyrosine phosphatase (HDPTP), plays in cell adhesion. Depletion of Mop results in aberrant integrin distribution and border cell dissociation during Drosophila oogenesis. Interestingly, Mop phosphatase activity is not required for its role in maintaining border cell cluster integrity. Rab4 GTPase was further identified as a Mop interactor in a yeast two-hybrid screen. Expression of the Rab4 dominant-negative mutant leads to border cell dissociation and suppression of Mop-induced wing-blade adhesion defects, suggesting a critical role of Rab4 in Mop-mediated signaling. In mammals, it has been shown that Rab4-dependent recycling of integrins is necessary for cell adhesion and migration. This study found that human HDPTP regulates the spatial distribution of Rab4 and integrin trafficking. Depletion of HDPTP resulted in actin reorganization and increased cell motility. Together, these findings suggest an evolutionarily conserved function of HDPTP-Rab4 in the regulation of endocytic trafficking, cell adhesion and migration (Chen, 2012).
Cell adhesion and cell migration are essential for the development and coordinated function of multicellular organisms. Aberrant regulation of these processes often results in the progression of many diseases, including cancer invasion and metastasis. Accumulating evidence has indicated that dynamic and reversible protein tyrosine phosphorylation is essential for the regulation of cell migration and cell adhesion. While many studies have been devoted to the role of protein tyrosine kinases in these processes, the function of protein tyrosine phosphatases (PTPs) in cell adhesion and migration remains unclear (Chen, 2012).
The dynamic change of integrin-mediated focal adhesions plays a critical role in cell adhesion and migration. Many focal adhesion regulators such as focal adhesion kinase (FAK), Src, p130Cas, and paxillin are tyrosine phosphorylated. The tyrosine phosphorylation of these proteins affects focal adhesion dynamics. Phosphorylation of tyrosine 397 in FAK promotes its association with Src, and the activated FAK-Src complex subsequently regulates focal adhesion dynamics by signaling downstream targets. Several PTPs have been implicated in integrin signaling, cell adhesion and motility. One study has shown that SHP-2 phosphatase influences FAK activity. SHP-2 also promotes Src kinase activation by inhibiting Csk. Depletion of PTP-PEST has been found to lead to the hyperphosphorylation of p130Cas, FAK and paxillin, and a marked increase in focal adhesions. Moreover, PTP1B and PTPα, have also been found to regulate Src phosphorylation and integrin-mediated adhesion (Chen, 2012).
In Drosophila, a total of sixteen putative classical PTPs have been identified. Compared to mammalian PTPs, Drosophila PTP family members are relatively simple, most containing only one gene corresponding to each subtype (except for DPTP10D and DPTP4E, which share similar domain structures). Therefore, Drosophila can serve as an excellent model system for the study of the physiological and developmental function of PTPs. While much research has been devoted to the function of receptor PTPs, the role of non-transmembrane PTPs (NT-PTPs) in Drosophila development remains unknown. One of the most well studied Drosophila NT-PTPs is Corkscrew (Csw). Csw is the ortholog of human SHP-2 which has two SH2 domains at the N-terminus and a PTP domain at the C-terminus. Csw functions as a downstream effecter of Sevenless PTK and is essential for the development of the R7 photoreceptor. Phenotypic analysis showed that Csw can also act downstream of many receptor tyrosine kinases, such as the Drosophila epidermal growth factor receptor (DER) and the fibroblast growth factor (Breathless). PTP-ER has been shown to function as a negative regulator downstream of Ras1 and to be involved in RAS1/MAPK-mediated R7 photoreceptor differentiation. PTP61F, the Drosophila ortholog of human PTP1B and TCPTP, has been reported to interact with Dock, an adapter protein required for axon guidance. PTP61F has recent been shown to coordinate with dAbl in regulating actin cytoskeleton organization via reversible tyrosine phosphorylation of Abi and Kette ). Moreover, dPtpmeg, a FERM and PDZ domain-containing NT-PTP, is reported to be involved in the formation of neuronal circuits in the Drosophila brain, though its molecular function in this process is not known (Chen, 2012).
To explore the functional role of Drosophila NT-PTPs in cell adhesion and migration, genetic analyses was performed to identify NT-PTPs that could modulate border cell migration during oogenesis. This study found that Myopic (Mop), the Drosophila homolog of the human His domain phosphotyrosine phosphatase (HDPTP), plays an important role in maintaining border cell cluster integrity. Depletion of Mop altered the normal distribution of integrin receptor. While Mop has recently been reported to regulate EGFR and Toll receptor signaling (Miura, 2008; Huang, 2010), its molecular mechanism has remained elusive. This study found that Mop interacts with Rab4 GTPase in controlling integrin distribution and cell adhesion. It was further demonstrated that human HDPTP is essential for the intracellular positioning of Rab4, integrin trafficking, and cell migration. These findings provide some insight into the mechanisms underlying HDPTP in the regulation of cell adhesion and migration (Chen, 2012).
Accumulating evidence has indicated that vesicular trafficking regulates the distribution of plasma membrane content as well as the localization of cytoskeletal proteins during cell adhesion and migration. Drosophila border cells migrate as a cluster of strongly adherent cells during the development of the egg chamber. During this process, JNK signaling and endocytosis-mediated spatial distribution of receptor tyrosine kinases play a critical role, though mechanisms involved in this process have remained elusive. This identified Mop, the Drosophila homolog of human HDPTP, as a regulator of integrin trafficking. Mop is essential for proper integrin localization and for maintaining border cell integrity during oogenesis. It was further demonstrated that Mop and HDPTP interacts with Rab4 GTPase in both Drosophila and mammals. Rab4 has been shown to regulate integrin recycling and cell migration (Roberts, 2001; White, 2007). The current findings indicate that Mop/HDPTP-mediated endocytic trafficking plays an essential role in integrin-mediated cell adhesion and migration. Mop has been predicted as a nontransmembrane-PTP (Andersen, 2005). However, amino acid sequence analysis revealed that Mop displays several differences from conserved PTP motifs within the phosphatase domain. For example, the catalytic essential aspartic acid (D) within motif 8 (WPDXGXP) is replaced by a lysine residue (K). Although the active site cysteine (C) in the catalytic motif 9 (VHCSAGXGR[T/S]G) could be found, the overall signature motif of Mop was much more divergent compared to other PTPs. Moreover, no Mop tyrosine phosphatase activity could be detected using in vitro phosphatase assays. These results suggest that Drosophila Mop may not be enzymatic active. Alternatively, Mop may exhibit weak phosphatase activity which can not be detected using either pNPP or in gel phosphatase assay. A recent study by Lin (2011) indicated that human PTPN23/HDPTP exhibits relatively low activity that is comparable with the specific activity of PTP1B D181E mutant. This study also found that expression of Mop-C/S mutant, in which the catalytic cysteine in the active site is replaced by serine, or Mop phosphatase domain deletion mutant rescued the Mop-RNAi induced border cell dissociation defects as effectively as the wild-type Mop, indicating that the putative tyrosine phosphatase activity is not essential for maintaining border cell cluster integrity (Chen, 2012).
In addition to having a C-terminus phosphatase domain, Mop has a sequence similar to that of yeast Bro1 at the N-terminus. The Bro1 domain consists of a folded core of about 370 residues and has been found in many proteins, including Bro1, Cbl, indicating that it acts on internalized EGFR, and its overexpression enhances the activity of an activated form of EGFR. Myopic is localized to intracellular vesicles adjacent to Rab5-containing early endosomes, and its absence results in the enlargement of endosomal compartments. Loss of Myopic prevents cleavage of the EGFR cytoplasmic domain, a process controlled by the endocytic regulators Cbl and Sprouty. It is suggested that Myopic promotes EGFR signaling by mediating its progression through the endocytic pathway (Miura, 2008).
The Epidermal growth factor receptor (EGFR) is required for cell differentiation and proliferation in numerous developmental systems, and activation of the human EGFR homologs, ERBB1-4, is implicated in many cancers. EGFR signaling events are terminated following removal of the receptor from the cell membrane by endocytosis. Ubiquitylation of EGFR by Cbl, an E3 ubiquitin ligase, initiates its internalization into clathrin-coated vesicles and its transit through early and late endosomes, which differ by the exchange of Rab7 for Rab5. EGFR can either return to the cell surface in Rab11-containing recycling endosomes, or reach the lysosome for degradation. Delivery of receptors to the lysosome requires sorting from the limiting membrane of late endosomes into the internal vesicles of multivesicular bodies (MVBs), a process mediated by four endosomal sorting complexes required for transport (ESCRT-0, I, II and III). Ubiquitylated receptors are bound by Hepatocyte growth factor regulated tyrosine kinase substrate (Hrs) in ESCRT-0, Tumor susceptibility gene 101 (Tsg101; also known as Erupted) in ESCRT-I and Vacuolar protein sorting 36 (Vps36) in ESCRT-II, and their deubiquitylation and internalization are coordinated by ESCRT-III (Miura, 2008).
Genetic or pharmacological blocks of endocytosis prevent degradation of EGFR and other receptors. In Drosophila, Hrs mutations block MVB invagination, trapping receptor tyrosine kinases (RTKs) and other receptors on the outer membrane of the MVB, and sometimes leading to enhanced signaling. Mutations in the ESCRT complex subunits Tsg101 (ESCRT-I) and Vps25 (ESCRT-II) cause overproliferation owing to the accumulation of mitogenic receptors such as Notch and Thickveins. In mammalian cells, loss of Hrs (also known as Hgs) or Tsg101 results in increased EGFR signaling. However, other studies have demonstrated a positive role for endocytosis in receptor signaling. Mutations affecting the Drosophila trafficking protein Lethal giant discs dramatically increase Notch signaling only in the presence of Hrs, indicating that signaling is maximized at a specific point in the endocytic process. Wingless (Wg) signaling is enhanced by internalization into endosomes, where it colocalizes with downstream signaling molecules. In mammalian cells, EGFR encounters the scaffolding proteins Mek1 partner (Mp1) and p14, which are required for maximal phosphorylation of the downstream component mitogen-activated protein kinase (MAPK), only on endosomes (Miura, 2008).
The characterization of the novel Drosophila gene myopic (mop) is described here. Loss of mop affects EGFR-dependent processes in eye and embryonic development, and reduces MAPK phosphorylation by activated EGFR in cultured cells. Mop acts upstream of Ras activation to promote the function of activated, internalized EGFR. Mop is homologous to human HD-PTP (PTPN23 - Human Gene Nomenclature Database) (Toyooka, 2000), which contains a Bro1 domain that is able to bind the ESCRT-III complex component SNF7 (CHMP4B - Human Gene Nomenclature Database) (Ichioka, 2007; Kim, 2005) and a tyrosine phosphatase domain. Mop is present on intracellular vesicles, and cells lacking mop have enlarged endosomes and reduced cleavage of the EGFR cytoplasmic domain. It is proposed that Mop potentiates EGFR signaling by enhancing its progression through endocytosis. Consistent with this hypothesis, it was found that components of the ESCRT-0 and ESCRT-I complexes are also required for EGFR signaling in Drosophila cells (Miura, 2008).
This study shows that Mop is necessary for EGFR signaling in vivo and in cultured cells. Mop is located on endosomes and affects endosome size, promotes cleavage of EGFR and lysosomal entry of its ligand, and is not required in the absence of the Cbl or Sty proteins that regulate endocytic trafficking of EGFR. These data suggest that Mop enhances EGFR signaling by facilitating its progression through the endocytic pathway. Consistent with this model, Hrs and ESCRT-I subunits also have a positive effect on EGFR signaling (Miura, 2008).
The Bro1 domain of yeast Bro1 is sufficient for localization to late endosomes through its binding to the ESCRT-III subunit Snf7 (Kim, 2005), and this domain is present in many proteins involved in endocytosis. Bro1 itself is required for transmembrane proteins to reach the vacuole for degradation; it promotes protein deubiquitylation by recruiting and activating Doa4, a ubiquitin thiolesterase. Since mutations in the E3 ubiquitin ligase gene Cbl can rescue mop mutant clones, recruiting deubiquitylating enzymes might be one of the functions of Mop. The vertebrate Bro1-domain protein Alix (also known as AIP1 and Pdcd6ip) inhibits EGFR endocytosis by blocking the ubiquitylation of EGFR by Cbl, and by preventing the binding of Ruk (Sh3kbp1), which recruits endophilins, to the EGFR-Cbl complex. However, CG12876, not Mop, is the Drosophila ortholog of Alix (Miura, 2008).
A closer vertebrate homolog of Mop, which has both Bro1 and tyrosine phosphatase domains, has been named HD-PTP in human (Toyooka, 2000) and PTP-TD14 in rat. HD-PTP shares with Alix the ability to bind Snf7 and Tsg101, but does not bind to Ruk (Ichioka, 2007). PTP-TD14 was found to suppress cell transformation by Ha-Ras, and required phosphatase activity for this function (Cao, 1998). The activity of Mop described in this study appears distinct in that Mop acts upstream of Ras activation, and no requirement was demonstrated for the catalytic cysteine in its predicted phosphatase domain. If Mop does act as a phosphatase, Hrs would be a candidate substrate because tyrosine phosphorylation of Hrs by internalized receptors promotes its degradation, and Hrs levels appear reduced in mop mutant clones (Miura, 2008).
Endocytosis has been proposed to play several different roles in receptor signaling. Most commonly, endocytosis followed by receptor degradation terminates signaling. However, endocytosis can also prolong the duration of signaling or influence its subcellular location. Receptors may also signal through different downstream pathways localized to specialized endosomal compartments (Miura, 2008).
Genetic studies in Drosophila have emphasized the importance of endocytic trafficking for receptor silencing. Mutations in Hrs, Vps25 or Tsg101 result in the accumulation of multiple receptors on the perimeter membrane of the MVB, leading to enhanced signaling. Depletion of Hrs or Tsg101 in mammalian cells also results in increased EGFR signaling, although the two molecules have distinct effects on MVB morphology. By contrast, this study found that mop and Hrs mutants exhibit diminished EGFR signaling in vivo, and depletion of mop, Tsg101 or Vps28 reduces EGFR signaling in S2 cells. Progression through the endocytic pathway may thus be required for maximal EGFR signaling, at least in some contexts (Miura, 2008).
Several possible mechanisms could explain such a requirement for endocytic progression. MAPK phosphorylation may be enhanced in the presence of signaling components present on late endosomes. Cleavage of the EGFR cytoplasmic domain, which requires Mop activity, might enhance EGFR signaling. The cleaved intracellular domain of ErbB4 has been shown to enter the nucleus and regulate gene expression (Sardi, 2006), suggesting the possibility that Mop affects a nuclear function of EGFR in addition to promoting MAPK phosphorylation. Alternatively, the reduction in EGFR signaling in mop mutants could be due to a failure to recycle the receptor to the cell surface. Mutations in the yeast Vps class C genes, which are required for trafficking to late endosomes, also prevent the recycling of cargo proteins. Recycling is essential for EGFR-induced proliferation of mammalian cells, and may promote the localized RTK signaling that drives directional cell migration (Miura, 2008).
Despite the reduction in EGFR signaling in mop mutants, signaling by other receptors such as Notch, Smoothened and Torso is unaffected. This phenotypic specificity could be due to a dedicated function of Mop in the EGFR pathway, or to high sensitivity of EGFR signaling to a general process that requires Mop. Although the Mop-related protein Alix has been found in a complex with EGFR (Schmidt, 2004), no physical interaction of Mop with EGFR could be detected. The function of mop is not limited to promoting EGFR signaling; it also promotes trafficking of Wg and expression of the Wg target gene sens. In addition, mop is required for normal cellularization of the embryo, and its cellularization phenotype is not rescued by removal of Cbl (data not shown) (Miura, 2008). Additional studies will be required to determine whether all endosomes, or only a specific subclass, are affected by mop. Interestingly, EGF treatment of mammalian cells induces EGFR trafficking through a specialized class of MVBs. Although significant colocalization of activated EGFR with Mop was not seen, EGFR may transiently pass through Mop-containing endosomes before accumulating in another compartment. The wing disc appears less sensitive than the eye disc to the effect of mop on EGFR signaling. This might be due to differences in the endogenous levels of Cbl or other mediators of EGFR internalization, or in the strength or duration of signaling necessary to activate target genes, or to the use of a different ligand with distinct effects on receptor trafficking (Miura, 2008).
Taken together, these results identify a positive role for progress through the endocytic pathway and for the novel molecule Mop in EGFR signaling in Drosophila. The importance of upregulation of the trafficking proteins Rab11a, Rab5a and Tsg101 for EGFR signaling in hepatomas and breast cancers highlights the potential value of specific effectors of EGFR endocytosis as targets for anti-cancer therapies (Miura, 2008).
Search PubMed for articles about Drosophila Myopic
Andersen, J. N., Del Vecchio, R. L., Kannan, N., Gergel, J., Neuwald, A. F. and Tonks, N. K. (2005). Computational analysis of protein tyrosine phosphatases: practical guide to bioinformatics and data resources. Methods 35: 90-114. PubMed ID:15588990
Cao, L., Zhang, L., Ruiz-Lozano, P., Yang, Q., Chien, K. R., Graham, R. M. and Zhou, M. (1998). A novel putative protein-tyrosine phosphatase contains a BRO1-like domain and suppresses Ha-ras-mediated transformation. J Biol Chem 273: 21077-21083. PubMed ID: 9694860
Chen, D. Y., Li, M. Y., Wu, S. Y., Lin, Y. L., Tsai, S. P., Lai, P. L., Lin, Y. T., Kuo, J. C., Meng, T. C. and Chen, G. C. (2012). The Bro1-domain-containing protein Myopic/HDPTP coordinates with Rab4 to regulate cell adhesion and migration. J Cell Sci 125: 4841-4852. PubMed ID:22825871
Doyotte, A., Mironov, A., McKenzie, E. and Woodman, P. (2008). The Bro1-related protein HD-PTP/PTPN23 is required for endosomal cargo sorting and multivesicular body morphogenesis. Proc Natl Acad Sci U S A 105: 6308-6313. PubMed ID:18434552
Gilbert, M. M., Tipping, M., Veraksa, A. and Moberg, K. H. (2011). A screen for conditional growth suppressor genes identifies the Drosophila homolog of HD-PTP as a regulator of the oncoprotein Yorkie. Dev Cell 20: 700-712. PubMed ID:21571226
Gingras, M. C., Zhang, Y. L., Kharitidi, D., Barr, A. J., Knapp, S., Tremblay, M. L. and Pause, A. (2009). HD-PTP is a catalytically inactive tyrosine phosphatase due to a conserved divergence in its phosphatase domain. PLoS One 4: e5105. PubMed ID:19340315
Grant, B. D. and Donaldson, J. G. (2009). Pathways and mechanisms of endocytic recycling. Nat Rev Mol Cell Biol 10: 597-608. PubMed ID:19696797
Huang, H. R., (2010). Endocytic pathway is required for Drosophila Toll innate immune signaling. Proc. Natl. Acad. Sci. 107(18): 8322-7. PubMed ID: 20404143
Ichioka, F., Takaya, E., Suzuki, H., Kajigaya, S., Buchman, V. L., Shibata, H. and Maki, M. (2007). HD-PTP and Alix share some membrane-traffic related proteins that interact with their Bro1 domains or proline-rich regions. Arch. Biochem. Biophys. 457: 142-149. PubMed ID: 17174262
Kagan, J. C., Su, T., Horng, T., Chow, A., Akira, S. and Medzhitov, R. (2008). TRAM couples endocytosis of Toll-like receptor 4 to the induction of interferon-beta. Nat Immunol 9: 361-368. PubMed ID: 18297073
Kim, J., Sitaraman, S., Hierro, A., Beach, B. M., Odorizzi, G. and Hurley, J. H. (2005). Structural basis for endosomal targeting by the Bro1 domain. Dev. Cell 8: 937-947. PubMed ID: 15935782
Lin, G., Aranda, V., Muthuswamy, S. K. and Tonks, N. K. (2011). Identification of PTPN23 as a novel regulator of cell invasion in mammary epithelial cells from a loss-of-function screen of the 'PTP-ome'. Genes Dev 25: 1412-1425. PubMed ID: 21724833
Mariotti, M., Castiglioni, S. and Maier, J. A. (2009a). Inhibition of T24 human bladder carcinoma cell migration by RNA interference suppressing the expression of HD-PTP. Cancer Lett 273: 155-163. PubMed ID:18835089
Mariotti, M., Castiglioni, S., Garcia-Manteiga, J. M., Beguinot, L. and Maier, J. A. (2009b). HD-PTP inhibits endothelial migration through its interaction with Src. Int J Biochem Cell Biol 41: 687-693. PubMed ID:18762272
Miura, G. I., Roignant, J. Y., Wassef, M. and Treisman, J. E. (2008). Myopic acts in the endocytic pathway to enhance signaling by the Drosophila EGF receptor. Development 135(11): 1913-22. PubMed ID: 18434417
Roberts, M., Barry, S., Woods, A., van der Sluijs, P. and Norman, J. (2001). PDGF-regulated rab4-dependent recycling of alphavbeta3 integrin from early endosomes is necessary for cell adhesion and spreading. Curr Biol 11: 1392-1402. PubMed ID:11566097
Sardi, S. P., Murtie, J., Koirala, S., Patten, B. A. and Corfas, G. (2006). Presenilin-dependent ErbB4 nuclear signaling regulates the timing of astrogenesis in the developing brain. Cell 127: 185-197. PubMed ID: 17018285
Schmidt, M. H., Hoeller, D., Yu, J., Furnari, F. B., Cavenee, W. K., Dikic, I. and Bogler, O. (2004). Alix/AIP1 antagonizes epidermal growth factor receptor downregulation by the Cbl-SETA/CIN85 complex. Mol. Cell. Biol. 24: 8981-8993. PubMed ID: 15456872
Stenmark, H. (2009). Rab GTPases as coordinators of vesicle traffic. Nat Rev Mol Cell Biol 10: 513-525. PubMed ID:19603039
Toyooka, S., Ouchida, M., Jitsumori, Y., Tsukuda, K., Sakai, A., Nakamura, A., Shimizu, N. and Shimizu, K. (2000). HD-PTP: A novel protein tyrosine phosphatase gene on human chromosome 3p21.3. Biochem. Biophys. Res. Commun. 278: 671-678. PubMed ID: 11095967
White, D. P., Caswell, P. T. and Norman, J. C. (2007). alpha v beta3 and alpha5beta1 integrin recycling pathways dictate downstream Rho kinase signaling to regulate persistent cell migration. J Cell Biol 177: 515-525. PubMed ID:17485491
date revised: 5 February 2013
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