0 3 Two two CD 4 12 distinct distinct JJ 13 18 forms form NNS 19 21 of of IN 22 28 active active JJ 29 42 transcription transcription NN 43 49 factor factor NN 50 54 CREB CREB NNP 55 56 ( ( ( 56 60 cAMP cAMP NNP 61 69 response response NN 70 77 element element NN 78 85 binding binding NN 86 93 protein protein NN 93 94 ) ) ) 94 95 . . . 97 106 Mammalian mammalian JJ 107 112 cells cell NNS 113 120 express express VBP 121 124 two two CD 125 133 distinct distinct JJ 134 139 forms form NNS 140 142 of of IN 143 156 transcription transcription NN 157 163 factor factor NN 164 168 CREB CREB NNP 169 170 ( ( ( 170 174 cAMP cAMP NNP 175 183 response response NN 184 191 element element NN 192 199 binding binding NN 200 207 protein protein NN 207 208 ) ) ) 209 213 that that WDT 214 217 are be VBP 218 228 apparently apparently RB 229 232 the the DT 233 241 products product NNS 242 244 of of IN 245 256 alternative alternative JJ 257 265 splicing splicing NN 266 268 of of IN 269 272 the the DT 273 277 CREB CREB NNP 278 282 gene gene NN 283 293 transcript transcript NN 293 294 . . . 295 298 The the DT 299 302 two two CD 303 311 proteins protein NNS 312 318 differ differ VBP 319 321 by by IN 322 323 a a DT 324 332 14-amino 14-amino JJ 333 337 acid acid NN 338 349 serine-rich serine-rich JJ 350 359 insertion insertion NN 360 367 present present JJ 368 370 in in IN 371 374 one one CD 375 377 of of IN 378 381 the the DT 382 386 CREB CREB NNP 387 395 isoforms isoform NNS 395 396 . . . 397 399 We we PRP 400 404 show show VBP 405 409 that that IN 410 414 both both CC 415 419 CREB CREB NNP 420 428 isoforms isoform NNS 429 432 are be VBP 433 442 expressed express VBN 443 445 in in IN 446 450 many many JJ 451 455 cell cell NN 456 461 types type NNS 462 465 and and CC 466 475 mammalian mammalian JJ 476 483 species specie NNS 483 484 . . . 485 489 Both both DT 490 496 encode encode VBP 497 505 proteins protein NNS 506 510 that that WDT 511 515 bind bind VBP 516 528 specifically specifically RB 529 531 to to TO 532 533 a a DT 534 538 cAMP camp NN 539 547 response response NN 548 555 element element NN 556 558 in in FW 559 564 vitro vitro FW 564 565 . . . 566 568 As as IN 569 577 expected expect VBN 578 581 for for IN 582 590 proteins protein NNS 591 593 of of IN 594 598 this this DT 599 604 class class NN 604 605 , , , 606 609 the the DT 610 614 CREB CREB NNP 615 623 proteins protein NNS 624 628 bind bind VBP 629 632 DNA dna NN 633 635 as as IN 636 642 dimers dimer NNS 642 643 . . . 644 648 Both both DT 649 657 proteins protein NNS 658 664 impart impart VBP 665 679 cAMP-regulated camp-regulated JJ 680 695 transcriptional transcriptional JJ 696 704 activity activity NN 705 707 to to TO 708 709 a a DT 710 722 heterologous heterologous JJ 723 734 DNA-binding dna-binding JJ 735 741 domain domain NN 741 742 , , , 743 750 showing show VBG 751 755 that that IN 756 760 cAMP camp NN 761 769 directly directly RB 770 779 modulates modulate VBZ 780 783 the the DT 784 799 transcriptional transcriptional JJ 800 811 stimulatory stimulatory JJ 812 820 activity activity NN 821 823 of of IN 824 828 CREB CREB NNP 828 829 . . . 830 833 The the DT 834 842 presence presence NN 843 845 of of IN 846 854 multiple multiple JJ 855 859 CREB creb NN 860 868 isoforms isoform NNS 869 873 with with IN 874 883 identical identical JJ 884 895 DNA-binding dna-binding JJ 896 909 specificities specificity NNS 910 913 but but CC 914 925 differences difference NNS 926 928 in in IN 929 932 the the DT 933 941 presumed presumed JJ 942 952 regulatory regulatory JJ 953 959 domain domain NN 960 966 raises raise VBZ 967 970 the the DT 971 982 possibility possibility NN 983 987 that that IN 988 992 CREB CREB NNP 993 1001 proteins protein NNS 1002 1005 may may MD 1006 1008 be be VB 1009 1013 able able JJ 1014 1016 to to TO 1017 1026 integrate integrate VB 1027 1035 distinct distinct JJ 1036 1046 regulatory regulatory JJ 1047 1054 signals signal NNS 1055 1057 at at IN 1058 1061 the the DT 1062 1067 level level NN 1068 1070 of of IN 1071 1075 gene gene NN 1076 1089 transcription transcription NN 1089 1090 . . .