Psychiatry related information on DAPP1

• Initially the birds displayed motor activity only during the 8-hour DAPP [1].
• Dependent personality disorder patients scored significantly higher on DAPP-BQ Insecure Attachment, and lower on DAPP Stimulus Seeking, Callousness, Intimacy Problems, and Conduct Problems compared to the healthy controls and all other patient groups [2].

High impact information on DAPP1

• Daily 20-hour encephalic photophases (DEPP), transmitted (hours 0 to 20) via chronically implanted light-conducting fibers to selected sites in the basal hypothalamus of male white-crowned sparrows, were superimposed on daily 8-hour (hours 0 to 8) external ambient photophases (DAPP) [1].
• To further define the role Bam32 plays in B cells, we generated Bam32-deficient DT40 cells [3].
• These Bam32(-/-) cells exhibited lower levels of B cell antigen receptor (BCR)-induced calcium mobilization with modest decreases in tyrosine phosphorylation of phospholipase C (PLC)gamma 2 [3].
• The B lymphocyte-associated adaptor protein 32 kD in size (Bam32) is expressed at high levels in germinal center (GC) B cells [3].
• Activation of downstream transcription factors such as nuclear factor of activated T cells (NF-AT) and nuclear factor of kappa binding (NF-kappa B) was also impaired in Bam32(-/-) cells [3].

Biological context of DAPP1

• Src, Lyn and Lck tyrosine kinases phosphorylate DAPP1 at Tyr(139) in vitro at similar rates in the presence or absence of PtdIns(3,4,5)P(3), and overexpression of these kinases in HEK-293 cells induces the phosphorylation of Tyr(139) [4].
• We recently identified a novel adaptor protein, termed dual adaptor for phosphotyrosine and 3-phosphoinositides (DAPP1), that possesses a Src homology (SH2) domain and a pleckstrin homology (PH) domain [4].
• Taken together, these findings suggest that Bam32 functions to regulate BCR-induced signaling and cell survival most likely in germinal centers [3].
• We have identified and characterized a novel src homology 2 (SH2) and pleckstrin homology (PH) domain-containing adaptor protein, designated Bam32 (for B cell adaptor molecule of 32 kD). cDNAs encoding the human and mouse Bam32 coding sequences were isolated and the human bam32 gene was mapped to chromosome 4q25-q27 [5].
• We report the characterization of two signal transduction proteins related to Bam32, known as TAPP1 and TAPP2 [6].

Anatomical context of DAPP1

• These findings indicate that, following activation of PI 3-kinases, PtdIns(3,4,5)P(3) or PtdIns(3,4)P(2) bind to DAPP1, recruiting it to the plasma membrane where it becomes phosphorylated at Tyr(139) by a Src-family tyrosine kinase [4].
• Regulation of B-lymphocyte activation by the PH domain adaptor protein Bam32/DAPP1 [7].
• These results suggest that Bam32 regulates the cytoskeleton through Rac1 [8].
• The positive and negative effects of Bam32 variants on F-actin levels were closely mirrored by their effects on the activation of the GTPase Rac1, which is known to regulate actin remodeling in lymphocytes [8].
• BCR ligation induced colocalization of Bam32 with lipid rafts, clathrin, and actin filaments [9].

Associations of DAPP1 with chemical compounds

• These observations predict that DAPP1 will interact with both tyrosine phosphorylated proteins and 3-phosphoinositides and may therefore play a role in regulating the location and/or activity of such proteins(s) in response to agonists that elevate PtdIns(3,4,5)P(3) and PtdIns(3,4)P(2) [10].
• DAPP1: a dual adaptor for phosphotyrosine and 3-phosphoinositides [10].
• The structure is similar to the known structure of the PH domain of DAPP1 around the D-3 and D-4 inositol-phosphate-binding sites [11].
• Many of these proteins, such as protein kinase B, phosphoinositide-dependent kinase 1 and the dual adaptor for phosphotyrosine and 3-phosphoinositides (DAPP1) interact with both PtdIns(3,4,5)P(3) and PtdIns(3,4)P(2) with similar affinity [11].
• However, a glycine residue adjacent to the D-5 inositol-phosphate-binding site in DAPP1 is substituted for a larger alanine residue in TAPP1, which also induces a conformational change in the neighbouring residues [11].

Physical interactions of DAPP1

• Collectively, these findings indicate a novel role of Bam32 in connecting Src family PTKs to BCR internalization by an actin-dependent mechanism [9].

Other interactions of DAPP1

• These data suggest that Bam32 functions downstream of Src family PTKs to regulate BCR internalization [9].
• Bam32 contains one Src homology 2 and one pleckstrin homology domain and is phosphorylated at a single site, tyrosine 139 [8].
• The B lymphocyte adaptor molecule of 32 kDa (Bam32) is an adaptor that plays an indispensable role in BCR signaling [9].
• Strikingly, peroxide co-stimulation enhanced antigen receptor-induced membrane recruitment of Bam32 and TAPP2, with combined stimulation exceeding the maximum achievable with either stimulus alone [12].

Analytical, diagnostic and therapeutic context of DAPP1

• Bam32 is tyrosine-phosphorylated upon B cell antigen receptor (BCR) ligation or pervanadate stimulation and associates with phospholipase Cgamma2 [5].
• Two novel radioligands, N,N-dimethyl-2-(2-amino-4-methoxyphenylthio) b enzylamine (DAPP) and (N,N-dimethyl-2-(2-amino-4-cyanophenylthio) benzylamine (D ASB), were radiolabeled with carbon-11 and evaluated as in vivo probes of the serotonin transporter (SERT) using positron emission tomography (PET) [13].

References