MAFA
MAFA (Antigen da ke da alaƙa da aikin mast cell) wani nau'i ne na II membrane glycoprotein, wanda aka fara gano shi a saman ɓangarorin nau'in mast na mucosal na layin RBL-2H3 . Kwanan nan, an gano homologues na mutum da linzamin kwamfuta na MAFA duk da haka kuma (ko kawai) NK da T-cells sun bayyana. [1] MAFA yana da alaƙa da haɗin gwiwa tare da nau'in 1 Fcɛ masu karɓa a cikin ba kawai ƙwayoyin mast na mucosal na mutane da mice ba har ma a cikin sel mast serosal na waɗannan kwayoyin halitta guda ɗaya. [2]
 MAFA |
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Yana da ikon yin aiki a matsayin duka tashar don ions na calcium tare da hulɗa tare da wasu masu karɓa don hana wasu matakai na salula. Aiki yana dogara ne akan tsarinsa na musamman, wanda ya ƙunshi abubuwa da yawa na musamman da jerin abubuwan da ke ba da damar gudanar da ayyukansa. [3]
Ganowa
gyara sasheBinciken gwaji
gyara sasheAn fara gano MAFA ta Enrique Ortega da Isra'ila Pecht a cikin 1988 yayin da suke nazarin nau'in 1 Fcɛ receptors (FcɛRI) da kuma tashoshin Ca <sup id="mwGQ">2 +</sup> da ba a sani ba wanda ya ba da damar waɗannan masu karɓa suyi aiki a cikin ƙwayar salula. Ortega da Pecht sun yi gwaji ta hanyar amfani da jerin ƙwayoyin rigakafi na monoclonal akan layin RBL -2H3 na ƙwayoyin mast na bera. Yayin gwaji da ƙoƙarin nemo takamaiman maganin rigakafi wanda zai ɗaga amsa, an nuna G63 monoclonal antibody don tada martani ta hanyar hana ɓoyayyun ƙwayoyin salula waɗanda ke da alaƙa da masu karɓar FcɛRI a cikin waɗannan ƙwayoyin mucosal mast na bera. G63 antibody da aka haɗe zuwa takamaiman furotin mai karɓar membrane wanda ya haifar da tsarin hanawa ya faru. Musamman, hanawar ta faru ta hanyar G63 antibody da glycoprotein giciye-haɗin kai ta yadda hanyoyin samar da matsakanci na kumburi, Ciwon Ca2 + a cikin tantanin halitta, da hydrolysis na phosphatidylinositides duk an dakatar da su. Wannan ya haifar da hana ƙwayoyin cuta na amsawar FcɛRI ta al'ada. An ware furotin mai karɓar furotin da aka gano sannan aka yi nazarin inda aka gano cewa lokacin da aka haɗa haɗin kai, furotin a zahiri yana da canji mai daidaituwa wanda ya keɓance masu karɓar FcɛRI. Dangane da waɗannan sakamakon, Ortega da Pecht duka sun ba wa wannan sabuwar sunadarin sunadarin Mast cell mai alaƙa da antigen ko MAFA a takaice. [2]
Tsari da coding
gyara sasheTsarin sunadaran
gyara sasheTsarin gabaɗaya
gyara sasheAn ce MAFA shine nau'in glycoprotein membrane na II, wanda ke nufin cewa N-terminus zai fuskanci cytosol yayin da C-terminus zai fuskanci yanayin waje. Sunadaran yana da tsayin amino acid 188 kuma yana da yankuna hydrophobic da hydrophilic a cikin waɗannan amino acid. Sunan furotin na MAFA yana auna tsakanin 28 da 40 kilodaltons kuma yana iya kasancewa a matsayin duka monomer ko homodimer a cikin nau'ikan nau'ikan nau'ikan nau'ikan nau'ikan nau'ikan nau'ikan nau'ikan nau'ikan nau'ikan nau'ikan nau'ikan nau'ikan nau'ikan nau'ikan suna gani kamar yadda sakamakon SDS-PAGE ya gani wanda ke nuna manyan makada guda biyu dangane da waɗannan nau'ikan guda biyu. [2] Ma'auni na MAFA core polypeptide yana da nauyin kilodaltons 19, duk da haka, adadi mai yawa na nauyin ya fito ne daga oligosaccharides N-linked wanda aka haɗe akan furotin. Wannan glycosylation mai nauyi abu ne na kowa a tsakanin nau'in glycoproteins na membrane na II kuma shine maɓalli na duka tsarin su da aikinsu. Bambancin tsakanin matakan glycosylation yana taimakawa taka muhimmiyar rawa a cikin kaddarorin sunadaran MAFA, don haka furotin dole ne a yi shi da kyau kuma a gyara shi don samun cikakken aiki. [4]
Yankin CRD
gyara sasheC-terminus na MAFA ya ƙunshi amino acid 114 kuma yana da yanki na musamman da ake kira yankin ganewar carbohydrate, ko CRD a takaice. Wannan yanki, kamar yadda ake nunawa a cikin sunan, shine inda ake gane nau'ikan carbohydrates da kwayoyin sigina kuma suna manne da furotin. Wannan CRD yana cikin sauran glycoproteins da yawa da ke cikin eukaryotes mafi girma. An bambanta CRD da jerin amino acid 15 da aka kiyaye wanda ya haɗa da adadin amino acid masu zuwa: ragowar glycine guda biyu, ragowar leucine guda biyu, ragowar tryptophan biyar, da ragowar cysteine guda shida. Waɗannan ragowar suna taimakawa ƙirƙirar motif iri-iri ta hanyar hulɗar su gami da duka WIGL da CYYF motifs. [4]
Yankin cikin salula
gyara sasheTare da jeri na musamman akan duka N terminus da C terminus, yankin intracellular na wannan sunadaran yana ƙunshe da jerin na musamman da ake kira jerin SIYSTL, inda sunan shine taƙaitaccen amino acid harafi ɗaya na ragowarsa. [5] Duk amino acid ɗin da ke cikin wannan jeri na polar ne a cikin yanayi kuma ana ɗaukar su a matsayin wani ɓangare na Immunoreceptor Tyrosine-based Inhibitory Motif (ITM) . Wannan ITIM yana ba da damar furotin mai karɓa na MAFA ba kawai za a yi la'akari da nau'in glycoprotein na II ba, amma kuma an rarraba shi azaman mai karɓar mai hanawa. [5]
Rubutun kwayoyin halitta
gyara sasheRubutu da lambar fassarar
gyara sasheKamar yadda yake tare da sauran sunadaran, MAFA tana jujjuya rubuce-rubucen biyu tare da fassarar da gyare-gyaren fassarar bayan fassarori a cikin ER da Golgi. Yankin codeing na wannan furotin ya ƙunshi kilobytes 13 na bayanan kwayoyin halitta tare da exons biyar waɗanda aka raba ta intron huɗu a cikin kwayar halitta. Daga cikin waɗannan exons biyar, ana amfani da uku don taimakawa lambar yankin CRD wanda aka ambata a baya. Hakanan ana sarrafa wannan kwayar halitta ta hanyar yanki mai haɓakawa wanda ke 664 basepairs daga farkon nucleotide na furotin. Kamar sauran sunadaran, ana kwafi kwayar halittar a wuraren farawa da yawa kuma a haɗa su cikin kwafin mRNA . [6]
Madadin splicing
gyara sasheBayan da aka rubuta lambar zuwa mRNA, an kuma gano madaidaicin MAFA don jujjuya wani zaɓi wanda ya ba da damar fassara nau'ikan furotin na MAFA daban-daban kuma ya haifar da yawancin bambance-bambancen da aka tattauna a baya. Ɗaya daga cikin nau'i na wannan lambar yana share sashin furotin na MAFA kuma yana haifar da wani nau'i mai narkewa, kasancewa na musamman ga wannan furotin kuma ya ba wa masana kimiyya damar amfani da wannan madadin ra'ayi na daban ga sauran sunadaran Mast cell transmembrane. [4] Da zarar an fassara shi, sunadaran suna shiga hanyoyin salula masu dacewa daga ER zuwa Golgi kuma a ƙarshe membrane na salula, inda aka haɗa shi kuma ya fara aikinsa.
Aiki
gyara sasheAyyukan tashar
gyara sasheKamar yadda Ortega da Pecht suka gano, ɗayan manyan ayyuka na MAFA shine yin aiki azaman tashar Ca 2+ kamar yadda aka gani a cikin gwajin su tare da hana Ca 2+ lokacin da G63 antibody ya ɗaure zuwa yankin mai karɓar MAFA. Bugu da ƙari, kamar yadda aka gani ta gaskiyar cewa nau'in glycoprotein membrane ne na II kuma ta ikonsa na canza daidaituwa don ba da damar adadin adadin calcium shiga cikin tantanin halitta, MAFA kuma yana aiki azaman kwayar mai karɓa kuma yana iya hana matakai daban-daban a cikin ƙwayoyin mast. . Musamman, wannan hanawa ya kasance a cikin sashi saboda SIYSTL motif a C-terminus na furotin, wanda ke cikin matrix extracellular. Wannan tsarin yana da yawa tare da ragowar Tyrosine, wasu daga cikinsu suna da phosphorylated. Halin phosphorylation akan waɗannan ragowar suna taka muhimmiyar rawa wajen ƙyale MAFA ta hana matakai daban-daban na biochemical. [4]
Tari
gyara sasheFcɛRI
gyara sasheHakanan sunadaran MAFA suna hulɗa sosai tare da masu karɓa na FcɛRI ta hanyar samuwar tari da rafukan lipid a cikin membrane na salula. Ta hanyar samar da waɗannan jimillar tsarin, ana canza tsarin MAFA ta yadda zai iya yin hulɗa tare da masu karɓar FcɛRI don haka ba zai iya ɗaure tare da G63 monoclonal antibodies ba kuma an hana shi barin barin yaduwa a cikin membrane. Tare da hana aikin MAFA, mai karɓar FcɛRI kuma an hana shi, ma'ana cewa ko da an ɗaure wani abin ƙarfafawa ga mai karɓa, FcɛRI ba zai haifar da hydrolysis na phosphatidylinositides kamar yadda ya saba yi ba. [3] Sabili da haka, ta hanyar samar da waɗannan manyan gungu, duka ayyukan MAFA da FcɛRI masu karɓa an hana su kuma zasu iya haifar da ƙarin hanawa na tsarin siginar salula a cikin tantanin halitta. Ko da lokacin da MAFA ba ta haifar da yin hulɗa tare da FcɛRI ba, ƙwayar mast cell yana da hulɗar dabi'a tsakanin waɗannan masu karɓa guda biyu wanda ke haifar da ƙananan ƙwayoyin MAFA-FcɛRI ba tare da manyan canje-canje ga kowane ɗayan ayyukansu ba. [6] Har yanzu ba a gano takamaiman hanyar da MAFA da FcɛRI ke hulɗa tare da tarawa ba har yanzu. [4]
Zagayen salula
gyara sasheTare da yin hulɗa tare da wasu sunadaran, MAFA na iya samar da tari wanda ya ƙunshi kanta kawai, waɗanda ko dai monoclonal antibody G63, wanda ke da hannu a cikin bincikensa, ko kuma ta wasu sassan F (ab') 2 antibody da ke ɗaure ga hadaddun tantanin halitta. . Ta hanyar kafa waɗannan ƙungiyoyin MAFA, an gano cewa yana haifar da hana tsarin sake zagayowar tantanin halitta da hana mitosis ko Kwafi na DNA daga faruwa. [5] Musamman, wannan samuwar yana haifar da karuwa a cikin tyrosine phosphorylation na cyclins daban-daban da sunadaran da ke cikin tsarin tantanin halitta. Babban sunadaran sunadarai guda biyu waɗanda suke da phosphorylated sune p62 DOK da inositol phosphatase SHIP kuma wannan yana haifar da ƙarin canje-canjen hanyoyin da waɗannan sunadaran ke ciki. Don p62 DOK, tsarin phosphorylation yana haifar da ƙara haɓakawa zuwa RasGAP, wanda ke aiki don hana aikin gina jiki na Ras ta hanyar haifar da ayyukan GTPase da kuma GDP da za a ɗaure, wanda ya hana aikin Ras. Ta hanyar hana Ras, ci gaba da inganta rubutun DNA kuma an dakatar da shi, wanda ya haɗa da wasu sunadaran sake zagayowar tantanin halitta. [5] Don inositol phosphatase SHIP, phosphorylation ya haifar da ƙara yawan adadin dauri zuwa Shc, wanda aka saba da shi a ɗaure zuwa Sos1 yayin hawan keke. Sos1 da SHIP duka suna ɗaure ga Shc da gasa kuma ta hanyar haɓaka alaƙar Shc yayin phosphorylation, ɗaurin Sos1 yana raguwa sosai. Wannan dangantakar tana nuna cewa ragewar Sos1 shima yana da alaƙa da dakatar da zagayowar tantanin halitta, kodayake ba a gano hanyar da wannan hanawa ke faruwa ba. [5]
Madadin siffofin
gyara sasheHakanan MAFA na iya kasancewa ta nau'i-nau'i da yawa saboda madadin rarrabuwa da ɗayan waɗannan nau'ikan a cikin nau'in furotin mai narkewa inda ba a fassara da gyaggyarawa sashinsa na transmembrane. Wannan nau'i na MAFA na iya yaduwa daga cikin membrane na salula da kuma cikin matrix extracellular ba tare da lalacewa ko rushewa ta hanyar lysosomes ba, ma'ana yana aiki a cikin kwayoyin jikin mutum. Matsayin glycosylation tare da takamaiman aikin waɗannan sunadaran har yanzu ba a gano su ba, amma ana tsammanin cewa suna taka muhimmiyar rawa wajen taimakawa kula da matakan calcium tare da iyakance samuwar masu shiga tsakani a cikin waɗannan ƙwayoyin mast. [1] Ba a gano da yawa game da waɗannan madadin sifofin ba tukuna.
Magana
gyara sashe- ↑ 1.0 1.1 Abramson; Jakub Abramson; Rong Xu; Israel Pecht (September 2002). "An unusual inhibitory receptor—the mast cell function-associated antigen (MAFA)". Molecular Immunology. 38 (16–18): 1307–1313. doi:10.1016/S0161-5890(02)00080-9. PMID 12217400. Cite error: Invalid
<ref>tag; name "NAME2" defined multiple times with different content - ↑ 2.0 2.1 2.2 Ortega E, Schneider H, Pecht I. Possible interactions between the Fc epsilon receptor and a novel mast cell function-associated antigen. Int Immunol. 1991 Apr;3(4):333-42. doi: 10.1093/intimm/3.4.333. PMID 1831652.
- ↑ 3.0 3.1 Bocek P Jr, Guthmann MD, Pecht I. Analysis of the genes encoding the mast cell function-associated antigen and its alternatively spliced transcripts. J Immunol. 1997 Apr 1;158(7):3235-43. PMID 9120279.
- ↑ 4.0 4.1 4.2 4.3 4.4 Xu R, Pecht I. The mast cell function-associated antigen, a new member of the ITIM family. Curr Top Microbiol Immunol. 1999;244:159-68. doi: 10.1007/978-3-642-58537-1_14. PMID 10453658.
- ↑ 5.0 5.1 5.2 5.3 5.4 Abramson J, Pecht I. Clustering the mast cell function-associated antigen (MAFA) leads to tyrosine phosphorylation of p62Dok and SHIP and affects RBL-2H3 cell cycle. Immunol Lett. 2002 Jun 3;82(1-2):23-8. doi: 10.1016/s0165-2478(02)00013-5. PMID 12008030.
- ↑ 6.0 6.1 Song, Jinming; Hagen, Guy; Smith, Steven M. L.; Roess, Deborah A.; Pecht, Israel; Barisas, B. George (2002). "Interactions of the mast cell function-associated antigen with the type I Fcepsilon receptor". Molecular Immunology. 38 (16–18): 1315–1321. doi:10.1016/s0161-5890(02)00081-0. ISSN 0161-5890. PMID 12217401. Cite error: Invalid
<ref>tag; name ":4" defined multiple times with different content