Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.6.4.4 (kinesin)
 5,033 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The interaction of different protein systems with microtubules is a critical step in the cellular function of these organelles. The family of microtube-associated proteins (MAPs) together with a set of motor proteins such as kinesin, cytosolic dynein and dynamin are among the most clear examples of microtubule-interacting proteins. In addition, an increasing number of recently discovered proteins have been shown to interact with microtubules, even though they do not remain associated after cycles of assembly and disassembly. By using affinity columns of agarose derivatized with peptides from the C-terminal regulatory domain on tubulin, we found a 90 kDa protein that interacts with tubulin and microtubules. This protein, here designated as Mip-90, was isolated from neuroblastoma N2A and HeLa cells. It was also identified in high-speed supernatants of the neuroblastoma N-115, and non-neuronal cell lines NIH 3T3, Huh-7, HTB-145 and SW-13 vim+. Mip-90 was able to specifically bind to affinity columns of the agarose-bound beta-II(422-434) and beta-II(434-443) tubulin peptides, containing the sequences of MAP binding domains on beta-II-tubulin. Specific antibodies to Mip-90 along with an anti-beta-tubulin antibody used in double immunofluorescence experiments revealed a striking colocalization of this protein with the microtubule network. Nocodazole-treated cells showed significant changes in Mip-90 distribution as correlated to disruption of the microtubule cytoskeleton. On the other hand, Mip-90 colocalized with microtubule bundles with a perinuclear distribution in HeLa cells treated with taxol. The binding of Mip-90 to microtubules was confirmed by cosedimentation experiments. This protein also exhibited a strong affinity for a calmodulin-agarose affinity matrix, and a preparation of Mip-90 isolated by this affinity procedure was able to promote in vitro tubulin assembly into microtubules. The capacity of Mip-90 to interact with microtubules and with calmodulin suggested functional similarities to tau proteins. However, Western blot analysis using a polyclonal antibody against this protein revealed no cross-reactivity of Mip-90 with tau components. In addition, the 90 kDa protein is a thermosensitive protein. On the other hand, site-directed antibodies that recognize a repetitive binding domain on tau, MAP-2 and MAP-4 failed to react with Mip-90. The studies suggest that Mip-90, a microtubule-interacting protein incorporates into microtubules in vitro, and may play a role in modulating microtubule assembly and organization in non-neuronal cells, thus contributing to the regulation of the dynamics of the cytoskeletal network.
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PMID:Identification of a new microtubule-interacting protein Mip-90. 766 57

Prolactin induces maturation of insulin secretion in cultured neonatal rat islets. In this study, we investigated whether the improved secretory response to glucose caused by prolactin involves alteration in the expression, association and phosphorylation of several proteins that participate in these processes. Messenger RNA was extracted from neonatal rat islets cultured for 5 days in the presence of prolactin and reverse transcribed. Gene expression was analyzed by semi-quantitative RT-PCR and by Western blotting for proteins. The gene transcription and protein expression of kinesin and MAP-2 were increased in prolactin-treated islets compared to the controls. The association and phosphorylation of proteins was analyzed by immunoprecipitation followed by Western blotting, after acute exposure to prolactin. Prolactin increased the association between SNARE proteins and kinesin/MAP-2 while the association of munc-18/syntaxin 1A was decreased. Serine phosphorylation of SNAP-25, syntaxin 1A, munc-18, MAP-2 was significantly higher whereas kinesin phosphorylation was decreased in prolactin-treated islets. There was an increase in SNARE complex formation in islets stimulated with prolactin, 22 mM glucose, 40 mM K(+), 200 microM carbachol and 1 microM PMA. The prolactin-induced increase in the formation of SNARE complex and syntaxin 1A phosphorylation was inhibited by PD098059 and U0126, inhibitors of the MAPK pathway. These findings indicate that prolactin primes pancreatic beta-cells to release insulin by increasing the expression and phosphorylation/association of proteins implicated in the secretory machinery and the MAPK/PKC pathway is important for this effect.
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PMID:Prolactin modulates the association and phosphorylation of SNARE and kinesin/MAP-2 proteins in neonatal pancreatic rat islets. 1757 85