Open AccessFunctional analysis of the guanylate kinase‐like domain in the synapse‐associated protein SAP97
Author(s) -
Kuhlendahl Sven,
Spangenberg Oliver,
Konrad Manfred,
Kim Eunjoon,
Garner Craig C.
Publication year - 1998
Publication title -
european journal of biochemistry
Language(s) - English
Resource type - Journals
eISSN - 1432-1033
pISSN - 0014-2956
DOI - 10.1046/j.1432-1327.1998.2520305.x
Subject(s) - guanylate kinase , microbiology and biotechnology , guanine nucleotide exchange factor , sh3 domain , biology , protein kinase domain , gtp' , kinase , biochemistry , signal transduction , chemistry , enzyme , proto oncogene tyrosine protein kinase src , membrane protein , gene , membrane , mutant
SAP97 is a membrane cytoskeletal protein localized at the presynaptic nerve terminals of type 1 asymmetric synapses. It has been implicated in the assembly of synapses and in particular in the localization and clustering of ion channels. The C‐terminal GK domain of SAP97 shares a high degree of sequence similarity with low‐molecular‐mass guanylate kinases. These enzymes are involved in the guanine nucleotide metabolic cycle and in the maintenance of GTP/GDP pools required for example in Ras‐mediated cell signaling. It has therefore been hypothesized that SAP97 plays an essential role in cellular signaling by regulating the guanine nucleotide pools at synaptic junctions. Here, we test this hypothesis by assessing whether the GK domain in SAP97 encodes an authentic guanylate kinase. We show that the GK domain in and of itself does not encode an active guanylate kinase, that it cannot be activated by its binding partner GKAP and that flanking regions are not acting as inhibitory regulators for enzymatic activity. Thus, it would appear that the GK domain of SAP97 is not involved in the metabolism of guanine nucleotides required for signaling events.