Schematic of four hNUMB isoforms and amino acid sequence of the numb PTB^L PRR^L isoform (L, long; S, short). In bold are the amino acids inserted as a result of the alternative splicing of the human Numb transcript. Underlined are the potential SH3-binding sites denoted by the sequence PXXP.

Misexpression of hNUMB isoforms during sensory organ precursor development in Drosophila. (A) Wild-type wing margin. (B) Expression of hNUMB PRR^S at the dorsoventral margin of P[UAS-hNumbPRR^S] transgenic larval wing imaginal discs results in a dramatic loss of marginal hairs (>87%). (C) Expression of hNUMB PRR^L at the dorsoventral margin results in a significantly lower loss of marginal hairs (<20%). (Insets) Enlargements of the wing margin.

Tissue distribution of NUMB PRR^S- and PRR^L-encoding transcripts in adult tissues and human cancer cell lines. (A) Northern blots of rat tissues and human cancer cell lines were analyzed for PPR^S and PRR^L-specific mRNA expression. Lanes 1–8 are as follows: spleen, thymus, prostrate, testis, uterus, small intestine, colon, and peripheral blood leukocytes. Lanes 9–16 are Hl-60, HeLa, k-56, molt-4, Raji, sw480, a549, g361. Expression of a 4-kb transcript is observed in all lanes for PRR^S isoforms, whereas PRR^L transcripts are restricted to prostate, testis, uterus, and colon and heavily expressed in sw480 (colon–rectal adenocarcinoma) and A549 (lung carcinoma). (B) Transcripts encoding NUMB isoforms are differentially expressed in developing brain. PCR amplification of cDNA from human fetal brain, human adult brain, and neural tissue from developing embryonic rat was carried out using primers that flank the PRR insertion. Thirty cycles of amplification revealed the existence of PRR^L transcripts in fetal but not adult brain. PCR products representing PRR^L transcripts were observed in rat neural tube at day 8, decreasing in intensity through development. No PRR^L transcripts were detected in embryonic day 6 rat head or human adult brain even after an additional five cycles of amplification.