Costal2, a Novel Kinesin-Related Protein in the Hedgehog Signaling Pathway

Sisson, John C.; Ho, Karen S.; Suyama, Kaye; Scott, Matthew P.

doi:10.1016/s0092-8674(00)80332-3

Cited by 315 publications

(261 citation statements)

References 63 publications

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“…However, the effects of cos2 loss of function can be examined in adult structures through mosaic analysis. Clones of cells in far anterior regions of the A compartment of the wing imaginal disc that lack cos2 trigger anterior overgrowth phenotypes, and activation of low level Hh target genes, suggesting a negative regulatory role [23,66,67,71]. However, cos2 clones near the A/P compartment boundary do not express high level Hh-target genes, suggesting a role for Cos2 in activation of Ci [48,66,71].…”

Section: Costal2mentioning

confidence: 99%

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Regulation of Hedgehog signaling: a complex story

Ogden

Ascano

Stegman

et al. 2004

Biochemical Pharmacology

102

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The Hedgehog (Hh) signal transduction pathway plays critical instructional roles during development. Activating mutations in human Hh signaling components predispose to a variety of tumor types, and have been observed in sporadic tumors occurring in a wide range of organs. Multiple insights into the regulation of Hh signaling have been achieved through studies using Drosophila melanogaster as a model organism. In Drosophila, regulation of the transcription factor

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Section: Costal2mentioning

confidence: 99%

“…Cos2 shares homology with the family of Kinesin-related protein (KRP) molecular motors [23]. KRPs bind vesicular membranes and microtubules (MT) in a highly regulated manner, and can facilitate movement along MTs through ATP hydrolysis (reviewed in [77]).…”

Section: Costal2mentioning

confidence: 99%

Regulation of Hedgehog signaling: a complex story

Ogden

Ascano

Stegman

et al. 2004

Biochemical Pharmacology

102

View full text Add to dashboard Cite

show abstract

“…More surprisingly, interactions may also take place that involve kinesins as the MLK2 kinase (5) or the tumor suppressor APC were shown to interact with the kinesin-like KIF3 (55). Cubitus interruptus is bound to the kinesin-related protein Costal 2 in the Hedgehog signaling pathway (56,57), and JIP scaffolding proteins for the JNK signaling pathway were found to bind conventional kinesin (58). Regarding the case of STAT5B, dynein-mediated trafficking along MTs is consistent with the fact that STAT5 and the GR may translocate together into the nucleus (34) and that the GR associates with the dynein intermediate chain (39).…”

Section: Figmentioning

confidence: 99%

STAT5B-mediated Growth Hormone Signaling Is Organized by Highly Dynamic Microtubules in Hepatic Cells

Phung-Koskas

Pilon

Poüs

et al. 2005

Journal of Biological Chemistry

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In the last decade, the notion that microtubules are critical to the spatial organization of signal transduction and contribute to the transmission of signals to downstream targets has been proposed. Because the STAT5B transduction and transcription factor is the major STAT protein activated by growth hormone stimulation in hepatocytes and is a crossroads between many signaling pathways, we studied the involvement of microtubules in STAT5B-mediated growth hormone signaling pathway in the highly differentiated and polarized WIF-B hepatic cell line. We showed that depolymerization of the microtubule network impaired STAT5B translocation to the nucleus upon growth hormone treatment. A significant amount of STAT5B binds to microtubules, while STAT5A and STAT3 are exclusively compartmentalized in the cytosol. Moreover, taxol-induced stabilization of microtubules released STAT5B from its binding, and we show that STAT5B binds specifically to the highly dynamic microtubules and is absent of the stable microtubule subpopulation. The specific involvement of dynamic microtubule subpopulation in growth hormone signaling pathway was confirmed by the inhibition of growth hormone-induced STAT5B nuclear translocation after stabilization of microtubules or specific disruption of highly dynamic microtubules. Upon growth hormone treatment, MT-bound STAT5B was rapidly released from microtubules by a dynein-dependent transport to the nucleus. Altogether, our findings indicate that the labile microtubule subpopulation specifically and dynamically organizes STAT5B-mediated growth hormone signaling in hepatic cells.Once bound to specific receptors, a large number of cytokines, growth factors, and hormones act through a sequence of steps allowing the rapid transport of information from the plasma membrane to subcellular targets. This information often results in the phosphorylation of transcription factors that subsequently migrate to the nucleus where they initiate specific gene transcription. How transcription factors are organized as molecular targets downstream of receptor activation and how they move rapidly through the cytoplasm from their activation site to the nucleus often remains unclear. The notion that microtubules (MTs) 1 might be involved in the cytoplasmic activation and/or trafficking of various transcription factors and protein kinases has emerged, as many signal transduction molecules, including transcription factors and protein kinases, have been shown to interact with MTs (1). For example, the glucocorticoid receptor was shown to colocalize with the MT network in mammalian cells (2, 3). The tumor suppressor protein p53 also uses MT tracks to migrate to the nucleus (4). Various protein kinases such as the MAP kinase kinase kinase MLK2 (5) or the MAP kinases ERK1 and ERK2 (6) were also shown to interact or to colocalize with MTs or with microtubule-associated proteins (7).In this study, we investigated the putative involvement of the MT network in GH signaling in the highly differentiated WIF-B hepatic cell line (8, 9...

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“…Epistatic relationships suggested that, in addition to hedgehog, other members of this pathway included patched, the serpentine membrane protein smoothened (smo; Alcedo et al, 1996;van den Heuvel and Ingham, 1996), the kinesinlike protein costal-2 (cos-2; Sisson et al, 1997), the serine/threonine kinase fused (fu; Preat et al, 1990), the novel protein suppressor of fused (Monnier et al, 1998), and the zinc ®nger transcription factor cubitus interruptus (ci; Orenic et al, 1990). Initial studies of this signalling pathway focused on the hedgehog molecule whose expression de®nes the development of many embryonic and adult structures in both the¯y and vertebrates.…”

Section: Hedgehog Signalling Pathwaymentioning

confidence: 99%