|dc.description.abstract||Background: Reversible interactions between the components of cellular signaling pathways allow for
the formation and dissociation of multimolecular complexes with spatial and temporal resolution and, thus,
are an important means of integrating multiple signals into a coordinated cellular response. Several
mechanisms that underlie these interactions have been identified, including the recognition of specific
docking sites, termed a D-domain and FXFP motif, on proteins that bind mitogen-activated protein kinases
(MAPKs). We recently found that phosphatidylinositol-specific phospholipase C-γ1 (PLC-γ1) directly binds
to extracellular signal-regulated kinase 2 (ERK2), a MAPK, via a D-domain-dependent mechanism. In
addition, we identified D-domain sequences in several other PLC isozymes. In the present studies we
sought to determine whether MAPK docking sequences could be recognized in other enzymes that
metabolize phosphatidylinositols (PIs), as well as in enzymes that metabolize inositol phosphates (IPs).
Results: We found that several, but not all, of these enzymes contain identifiable D-domain sequences.
Further, we found a high degree of conservation of these sequences and their location in human and mouse
proteins; notable exceptions were PI 3-kinase C2-γ, PI 4-kinase type IIβ, and inositol polyphosphate 1-
Conclusion: The results indicate that there may be extensive crosstalk between MAPK signaling and
signaling pathways that are regulated by cellular levels of PIs or IPs.||en_US