Saturday, August 31, 2013

ADAPTER PROTEINS: A CLASS OF "WILD GENES"

We have venture to define "wild genes" as class of genes that have multiple interactions leading to uncontrolled neoplastic processes.   A particular note has to be noted about Adapter proteins (ie.Gerb2)
The notion that their standard description suggests they do not have intrinsic enzymatic properties tend to minimize their actual role.  Indeed these genes act as "obligatory cofactors" in many cancers.  Kantarjian et al discussing Chronic Myeloid leukemia reported: "Many of these interactions are mediated through tyrosine phosphorylation and require binding of the BCR-ABL to adapter proteins such as the Grb2, CRK, CRK like proteins(CRKL), and SCR-homology containing proteins (SHC)".  In fact, downstream events will not effectively happen without these "enablers", making them an equal partner in crime.
Now going after these Adapters may prove dicey as it is assumed that they are also extensively found in normal tissue but who really knows until all phases of trials are completed.
Wikipedia:
"Signal transducing adaptor proteins are proteins which are accessory to main proteins in a signal transduction pathway. Adaptor proteins contain a variety of protein-binding modules that link protein-binding partners together and facilitate the creation of larger signaling complexes. These proteins tend to lack any intrinsic enzymatic activity themselves[1] but instead mediate specific protein–protein interactions that drive the formation of protein complexes. Examples of adaptor proteins include MyD88, Grb2 and SHC1."

and the list goes on:


Genes encoding adaptor proteins include:
  • BCAR3 – Breast cancer anti-estrogen resistance protein 3
  • GRAP – GRB2-related adaptor protein
  • GRAP2 – GRB2-related adaptor protein 2
  • LDLRAP1 – low density lipoprotein receptor adaptor protein 1
  • NCK1 – NCK adaptor protein 1
  • NCK2 – NCK adaptor protein 2
  • NOS1AP – nitric oxide synthase 1 (neuronal) adaptor protein
  • PIK3AP1 – phosphoinositide-3-kinase adaptor protein 1
  • SH2B1 – SH2B adaptor protein 1
  • SH2B2 – SH2B adaptor protein 2
  • SH2B3 – SH2B adaptor protein 3
  • SH2D3A -SH2 domain containing 3A
  • SH2D3C – SH2 domain containing 3C
  • SHB – Src homology 2 domain containing adaptor protein B
  • SLC4A1AP – solute carrier family 4 (anion exchanger), member 1, adaptor protein
  • GAB2 – GRB2-associated binding protein 2--wikipedia
Ignoring these "adapters" is a gross mistake
look at this one for example"

NSP1 Defines a Novel Family of Adaptor Proteins Linking Integrin and Tyrosine Kinase Receptors to the c-Jun N-terminal Kinase/Stress-activated Protein Kinase Signaling Pathway*

  1. Timothy A. Stewart
Basically this one tells you, without me c-JUN will not be stimulated and Neoplastic processes induced by prolonged c-JUN stimulation will not occur!
" In contrast, cell contact with fibronectin results in Cas phosphorylation and a transient dissociation of NSP1 from p130Cas. Increased expression of NSP1 in 293 cells induces activation of JNK1, but not of ERK2. Consistent with this observation, NSP1 increases the activity of an AP-1-containing promoter. Thus, we have described a novel family of adaptor proteins, one of which may be involved in the process by which receptor tyrosine kinase and integrin receptors control the c-Jun N-terminal kinase/stress-activated protein kinase pathway." an interesting observation, conclusion by the authors...

OF INTEREST ALSO IS THE BCAR3 IS PROPOSED IN THE RESISTANCE OF BREAST CANCERS TO TAMOXIFEN, IS IT A FACTOR OR MECHANISM OF DESENSITIZATION?

SUFFICE IS TO SAY THAT OUR EVOLVING UNDERSTANDING OF THESE ADAPTERS SHOULD BE OFTEN REVISITED. BECAUSE THEY ARE INDEED "WILD GENES"...

(ARE THEY THE REASONS FOR ALOPECIA OR SKIN/DERMATITIS  SIDE EFFECTS OF THERAPEUTIC DRUGS?-NAUGHTY OBSERVATION TO TEASE RESEARCHERS AROUND THE WORLD!)
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