SH2B adapter protein 1 (Pro-rich, PH and SH2 domain-containing signaling mediator) (PSM) (SH2 domain-containing protein 1B)
1_MNGAP 6_ SPEDG 11_ ASPSS 16_ PPLPP 21_ PPPPS 26_ WREFC 31_ ESHAR 36_ AAALD 41_ FARRF 46_ RLYLA 51_ SHPQY 56_ AGPGA 61_ EAAFS 66_ RRFAE 71_ LFLQH 76_ FEAEV 81_ ARASG 86_ SLSPP 91_ ILAPL 96_ SPGAE 101_ ISPHD 106_ LSLES 111_ CRVGG 116_ PLAVL 121_ GPSRS 126_ SEDLA 131_ GPLPS 136_ SVSSS 141_ STTSS 146_ KPKLK 151_ KRFSL 156_ RSVGR 161_ SVRGS 166_ VRGIL 171_ QWRGT 176_ VDPPS 181_ SAGPL 186_ ETSSG 191_ PPVLG 196_ GNSNS 201_ NSSGG 206_ AGTVG 211_ RGLVS 216_ DGTSP 221_ GERWT 226_ HRFER 231_ LRLSR 236_ GGGAL 241_ KDGAG 246_ MVQRE 251_ ELLSF 256_ MGAEE 261_ AAPDP 266_ AGVGR 271_ GGGVA 276_ GPPSG 281_ GGGQP 286_ QWQKC 291_ RLLLR 296_ SEGEG 301_ GGGSR 306_ LEFFV 311_ PPKAS 316_ RPRLS 321_ IPCSS 326_ ITDVR 331_ TTTAL 336_ EMPDR 341_ ENTFV 346_ VKVEG 351_ PSEYI 356_ METVD 361_ AQHVK 366_ AWVSD 371_ IQECL 376_ SPGPC 381_ PATSP 386_ RPMTL 391_ PLAPG 396_ TSFLT 401_ RENTD 406_ SLELS 411_ CLNHS 416_ ESLPS 421_ QDLLL 426_ GPSES 431_ NDRLS 436_ QGAYG 441_ GLSDR 446_ PSASI 451_ SPSSA 456_ SIAAS 461_ HFDSM 466_ ELLPP 471_ ELPPR 476_ IPIEE 481_ GPPTG 486_ TVHPL 491_ SAPYP 496_ PLDTP 501_ ETATG 506_ SFLFQ 511_ GEPEG 516_ GEGDQ 521_ PLSGY 526_ PWFHG 531_ MLSRL 536_ KAAQL 541_ VLTGG 546_ TGSHG 551_ VFLVR 556_ QSETR 561_ RGEYV 566_ LTFNF 571_ QGKAK 576_ HLRLS 581_ LNEEG 586_ QCRVQ 591_ HLWFQ 596_ SIFDM 601_ LEHFR 606_ VHPIP 611_ LESGG 616_ SSDVV 621_ LVSYV 626_ PSSQR 631_ QQEPT 636_ TSHDP 641_ PQPPE 646_ PPSWT 651_ DPPQP 656_ GAEEA 661_ SRAPE 666_ VAAAA 671_ AAAAK 676_ ERQEK 681_ EKAGG 686_ GGVPE 691_ ELVPV 696_ VELVP 701_ VVELE 706_ EAIAP 711_ GSEAQ 716_ GAGSG 721_ GDAGV 726_ PPMVQ 731_ LQQSP 736_ LGGDG 741_ EEGGH 746_ PRAIN 751_NQYSF
1: Adapter protein for several members of the tyrosine kinase receptor family. Involved in multiple signaling pathways mediated by Janus kinase (JAK) and receptor tyrosine kinases, including the receptors of insulin (INS), insulin-like growth factor 1 (IGF1), nerve growth factor (NGF), brain-derived neurotrophic factor (BDNF), glial cell line-derived neurotrophic factor (GDNF), platelet-derived growth factor (PDGF) and fibroblast growth factors (FGFs). In growth hormone (GH) signaling, autophosphorylated ('Tyr-813') JAK2 recruits SH2B1, which in turn is phosphorylated by JAK2 on tyrosine residues. These phosphotyrosines form potential binding sites for other signaling proteins. GH also promotes serine/threonine phosphorylation of SH2B1 and these phosphorylated residues may serve to recruit other proteins to the GHR-JAK2-SH2B1 complexes, such as RAC1. In leptin (LEP) signaling, binds to and potentiates the activation of JAK2 by globally enhancing downstream pathways. In response to leptin, binds simultaneously to both, JAK2 and IRS1 or IRS2, thus mediating formation of a complex of JAK2, SH2B1 and IRS1 or IRS2. Mediates tyrosine phosphorylation of IRS1 and IRS2, resulting in activation of the PI 3-kinase pathway. Acts as a positive regulator of NGF-mediated activation of the Akt/Forkhead pathway; prolongs NGF-induced phosphorylation of AKT1 on 'Ser-473' and AKT1 enzymatic activity. Enhances the kinase activity of the cytokine receptor-associated tyrosine kinase JAK2 and of other receptor tyrosine kinases, such as FGFR3 and NTRK1. For JAK2, the mechanism seems to involve dimerization of both, SH2B1 and JAK2. Enhances RET phosphorylation and kinase activity. Isoforms seem to be differentially involved in IGF1 and PDGF-induced mitogenesis (By similarity)