%0 Journal Article
%T The LIM and SH3 domain protein family: structural proteins or signal transducers or both?
%A Thomas GP Grunewald
%A Elke Butt
%J Molecular Cancer
%D 2008
%I BioMed Central
%R 10.1186/1476-4598-7-31
%X The LASP1 gene was initially identified together with three other genes from a cDNA library of metastatic axillary lymph nodes (MLN) from human breast cancer and therefore called MLN50. All four genes were mapped to chromosomal region 17q11-q21.3, a region known to contain the c-erbB-2 and the BRCA1 oncogene and to be altered in 20¨C30% of all breast cancers [1,2]. Northern blot analysis revealed that the approximately 4.0 kb long mRNA of MLN50 is ubiquitously expressed at basal levels in normal tissue and overexpressed in 8% of all tested human breast cancer tissues (5 of 61). Sequence analysis showed that MLN50 encoded a putative protein of 261 residues containing a LIM motif at its amino terminus and a src homology 3 (SH3) domain at its C-terminal part. This domain organization defined a new LIM protein subfamily characterized by the combined presence of LIM and SH3 domains [1]. MLN50 was termed accordingly: LIM and SH3 Protein 1 ¨C in short LASP-1.The LIM domain is an arrangement of eight cysteine and histidine residues (C-X2-C-X16/23-H-X2-C-X2-C-X2-C-X16/21-C-X2/3-C/D/H), is found in a number of vertebrate and invertebrate proteins and known to mediate protein-protein interactions as a modular binding interface [1,3-5]. Although no binding partner for the LIM-domain of LASP-1 has been identified so far, the zinc-finger module in the LIM-domain of LASP-1 is a morphologically and perhaps functionally independent folding-unit of this protein harbouring the possibility of direct binding to DNA [6].The N-terminal LIM domain is followed by two nebulin-like repeats called R1 and R2 each 35 residues long enabling the protein to bind to F-actin. The actin-binding domains of LASP-1 mediate a direct interaction between LASP-1 and actin at cell membrane extensions [7-12]. The binding of LASP-1 to actin stress fibres is mediated through its interaction with palladin that binds to the SH3 domain of LASP-1. siRNA knock-down of palladin leads to loss of LASP-1 at actin stress fi
%U http://www.molecular-cancer.com/content/7/1/31